Amyloid Beta and Phosphorylated Tau-Induced Defective Autophagy and Mitophagy in Alzheimer’s Disease
Open accessAbstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and multiple cognitive impairments. Several decades of intense research have revealed that multiple cellular changes are implicated in the development and progression of AD, including mitochondrial damage, synaptic dysfunction, amyloid beta (Aβ) formation and accumulation, hyperphosphorylated tau (P-Tau) formation and accumulation, deregulated microRNAs, synaptic damage, and neuronal loss in patients with AD. Among these, mitochondrial dysfunction and synaptic damage are early events in the disease process. Recent research also revealed that Aβ and P-Tau-induced defective autophagy and mitophagy are prominent events in AD pathogenesis. Age-dependent increased levels of Aβ and P-Tau reduced levels of several autophagy and mitophagy proteins. In addition, abnormal interactions between (1) Aβ and mitochondrial fission protein Drp1; (2) P-Tau and Drp1; and (3) Aβ and PINK1/parkin lead to an inability to clear damaged mitochondria and other cellular debris from neurons. These events occur selectively in affected AD neurons. The purpose of our article is to highlight recent developments of a Aβ and P-Tau-induced defective autophagy and mitophagy in AD. This article also summarizes several aspects of mitochondrial dysfunction, including abnormal mitochondrial dynamics (increased fission and reduced fusion), defective mitochondrial biogenesis, reduced ATP, increased free radicals and lipid peroxidation, and decreased cytochrome c oxidase (COX) activity and calcium dyshomeostasis in AD pathogenesis. Our article also discusses how reduced levels of Drp1, Aβ, and P-Tau can enhance the clearance of damaged mitochondria and other cellular debris by autophagy and mitophagy mechanisms.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Disruption of autophagic flux and failure of autophagosomes to fuse with lysosomes result in accumulation of vesicles observed in dystrophic neurites and cell bodies in tauopathy models.
“The disruption of the autophagic flux and the failure of autophagosomes to fuse with lysosomes result in the accumulation of vesicles, which can be observed in dystrophic neurites and cell bodies in tauopathy models [27,28,29].”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [28]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
3 retracted
Mańczak, M., Kandimalla, R. J. L., Yin, X., & Reddy, P. H. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy042 · Cited by 290 · cited 4× · see citing works
“In their next study, the Reddy group [73] investigated Aβ-induced mitochondrial, synaptic, autophagy, mitophagy, synaptic activities, and cognitive behavior in 12-month-old APP transgenic mice.”
BackgroundInfluentialSelf-citationRetractedKandimalla, R. J. L., Mańczak, M., Yin, X., Wang, R., & Reddy, P. H. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx381 · Cited by 260 · cited 2× · see citing works
“Based on these observations, they propose that the hippocampal accumulation of phosphorylated tau is responsible for synaptic damage and hippocampal-based learning and memory impairments in tau mice [74].”
BackgroundSelf-citationRetractedKuruva, C. S., Mańczak, M., Yin, X., Ogunmokun, G., Reddy, A. P., & Reddy, P. H. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx226 · Cited by 71 · cited 2× · see citing works
“The final steps involve engulfment by an autophagosome, which then fuses membranes with a lysosome, destroying the mitochondrion [7,14,84,85].”
BackgroundSelf-citationRetractedRepertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · cited 1× · see citing works
“There is an element of inefficiency where electrons escape the electron carriers of the ETC to dioxygen molecules to form superoxide I [33,34].”
BackgroundMitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · cited 1× · see citing works
“The pathological features of AD include synaptic dysfunction, resultant cognitive impairment, and short-term memory loss, where persons are unable to formulate new memories [4,5].”
BackgroundCillà, S. D., Farruggio, S., Vujosevic, S., Raina, G., Filippini, D. A., Gatti, V., Clemente, N., Mary, D., Vezzola, D., Casini, G., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479441 · Cited by 5,154 · see citing works
Oxyl radicals, redox-sensitive signalling cascades and antioxidants
Genestra, M. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.04.009 · Cited by 4,930 · see citing works
Autophagy: cellular and molecular mechanisms
Glick, D. R., Barth, S., & Macleod, K. F. (2010) · The Journal of Pathology · doi:10.1002/path.2697 · Cited by 3,815 · cited 7× · see citing works
“In micro-autophagy, via invagination of its membrane the lysosome directly engulfs and degrades cytosolic components itself [79].”
BackgroundInfluentialHyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942 · see citing works
Tanida, I., Ueno, T., & Kominami, E. (2008) · Methods in Molecular Biology™ · doi:10.1007/978-1-59745-157-4_4 · Cited by 1,785 · cited 2× · see citing works
“Microtubule-associated protein 1A/1B-light chain 3 (LC3-1) is pervasive within mammalian tissues and even in-vitro cells, and plays an integral role in the autophagy pathway [99].”
BackgroundAlzheimer's Disease and the Amyloid-β Peptide
Murphy, M. P., & LeVine, H. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-1221 · Cited by 1,750 · cited 1× · see citing works
“amyloid-beta protein to a disease-causing conformation, phosphorylated tau damage, and resultant cellular and mitochondrial damage [49,50].”
BackgroundFang, E. F., Hou, Y., Palikaras, K., Adriaanse, B. A., Kerr, J. S., Yang, B., Lautrup, S., Hasan-Olive, M. M., Caponio, D., Dan, X., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0332-9 · Cited by 1,740 · cited 2× · see citing works
“Nonetheless, in severely chronic diseases such as AD, mitophagy is also impaired [48].”
BackgroundMitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells
Liu, L., Feng, D., Chen, G., Chen, M., Zheng, Q., Song, P., Ma, Q., Zhu, C., Wang, R., Qi, W., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2422 · Cited by 1,689 · cited 2× · see citing works
“FUNDC1 is a highly conserved protein, which localizes to mitochondria and binds to LC3-1, encouraging the mitochondrial autophagy pathway [100].”
BackgroundProduction of Reactive Oxygen Species by Mitochondria
Chen, Q., Vazquez, E. J., Moghaddas, S., Hoppel, C. L., & Lesnefsky, E. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304854200 · Cited by 1,616 · see citing works
Mechanisms of mitophagy in cellular homeostasis, physiology and pathology
Palikaras, K., Lionaki, E., & Tavernarakis, N. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0176-2 · Cited by 1,505 · cited 9× · see citing works
“This particular mitophagy pathway is descriptiv of stress-induced mitophagy [86].”
BackgroundInfluentialMitochondrial dynamics: overview of molecular mechanisms
Tilokani, L., Nagashima, S., Paupe, V., & Prudent, J. (2018) · Essays in Biochemistry · doi:10.1042/ebc20170104 · Cited by 1,397 · cited 4× · see citing works
“When a mitochondrion fuses membranes with another to form one large mitochondrion, it is called fusion [19,20].”
BackgroundInfluentialMitochondrial abnormalities in Alzheimer's disease
Hirai, K., Aliev, G., Nunomura, A., Fujioka, H., Russell, R. L., Atwood, C. S., Johnson, A. B., Kress, Y., Vinters, H. V., Tabaton, M., et al. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-09-03017.2001 · Cited by 1,367 · see citing works
ABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease
Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004) · Science · doi:10.1126/science.1091230 · Cited by 1,303 · see citing works
Generation of reactive oxygen species by the mitochondrial electron transport chain
Liu, Y., Fiskum, G., & Schubert, D. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00744.x · Cited by 1,260 · see citing works
The axonal transport of mitochondria
Saxton, W. M., & Hollenbeck, P. J. (2012) · Journal of Cell Science · doi:10.1242/jcs.053850 · Cited by 1,198 · see citing works
Essential role for Nix in autophagic maturation of erythroid cells
Sandoval, H., Thiagarajan, P., Dasgupta, S. K., Schumacher, A., Prchal, J. T., Chen, M., & Wang, J. (2008) · Nature · doi:10.1038/nature07006 · Cited by 1,185 · cited 1× · see citing works
“For example, NIP3-like protein X (NIX)-mediated mitophagy is necessary for the removal of mitochondria during erythropoiesis [92].”
BackgroundManczak, M., Anekonda, T. S., Henson, E., Park, B. S., Quinn, J., & Reddy, P. H. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl066 · Cited by 1,104 · cited 1× · see citing works
“In their next paper, Reddy and colleagues [55] tested their hypothesis in a series of experiments examining what forms of APP and Aβ localize to the mitochondria, and whether the presence of these species is associated with mitochondrial dysfunction and oxidative damage.”
BackgroundSelf-citationMitochondrial Dynamics — Mitochondrial Fission and Fusion in Human Diseases
Archer, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1215233 · Cited by 1,103 · cited 4× · see citing works
“When a mitochondrion fuses membranes with another to form one large mitochondrion, it is called fusion [19,20].”
BackgroundInfluentialChu, C. T., Ji, J., Dagda, R. K., Jiang, J. F., Tyurina, Y. Y., Kapralov, A. A., Tyurin, V. A., Yanamala, N., Shrivastava, I. H., Mohammadyani, D., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2837 · Cited by 1,083 · cited 1× · see citing works
“However, there is mitophagic dysfunction in AD [2,17].”
BackgroundYao, J., Irwin, R. W., Zhao, L., Nilsen, J., Hamilton, R. T., & Brinton, R. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903563106 · Cited by 940 · see citing works
NIX is required for programmed mitochondrial clearance during reticulocyte maturation
Schweers, R. L., Zhang, J., Randall, M. S., Loyd, M. R., Li, W., Dorsey, F. C., Kundu, M., Opferman, J. T., Cleveland, J. L., Miller, J. L., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708818104 · Cited by 939 · cited 2× · see citing works
“It is believed that the dysfunction of programmed mitophagy results in degeneration—particularly neurodegeneration, accelerated aging, mutations, and cancer [91].”
BackgroundDu, H., Guo, L., Fang, F., Chen, D., Sosunov, A. A., McKhann, G. M., Yan, Y., Wang, C., Zhang, H., Molkentin, J. D., et al. (2008) · Nature Medicine · doi:10.1038/nm.1868 · Cited by 935 · see citing works
Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration
Sheng, Z., & Cai, Q. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3156 · Cited by 906 · cited 7× · see citing works
“This in turn also contributes to synaptic dysfunction [16].”
BackgroundInfluentialMitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms
Kerr, J. S., Adriaanse, B. A., Greig, N. H., Mattson, M. P., Cader, M. Z., Bohr, V. A., & Fang, E. F. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.01.002 · Cited by 870 · cited 3× · see citing works
“The final steps involve engulfment by an autophagosome, which then fuses membranes with a lysosome, destroying the mitochondrion [7,14,84,85].”
BackgroundMitochondria and Mitochondrial Cascades in Alzheimer’s disease
Swerdlow, R. H. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170585 · Cited by 850 · cited 1× · see citing works
“, Huntington’s disease [39], amyotrophic lateral sclerosis [40], Parkinson’s disease [41], Friedreich ataxia [42], Alzheimer’s disease [43]), and chronic liver diseases (e.”
BackgroundWang, X., Su, B., Siedlak, S. L., Moreira, P. I., Fujioka, H., Wang, Y., Casadesus, G., & Zhu, X. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804871105 · Cited by 835 · see citing works
Mańczak, M., Calkins, M. J., & Reddy, P. H. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr139 · Cited by 830 · cited 6× · see citing works
“The final steps involve ngulf ent by an autophagosome, which then fuses membranes with a lysosome, destroying the mitochondrion [7,14,84,85].”
BackgroundInfluentialSelf-citationThe Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease
Swerdlow, R. H., & Khan, S. M. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2003.12.045 · Cited by 758 · see citing works
Richter, B., Sliter, D. A., Herhaus, L., Stolz, A., Wang, C., Beli, P., Zaffagnini, G., Wild, P., Martens, S., Wagner, S. A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1523926113 · Cited by 755 · cited 6× · see citing works
“Optineurin (OPTN) along with NDP52 (CALCOCO2), TAX1BP1, and p62 are utilized during mitophagy to adhere mitochondria and ubiquitinated proteins to autophagic membranes [98].”
BackgroundInfluentialMitochondrial dysfunction is a trigger of Alzheimer's disease pathophysiology
Moreira, P. I., Carvalho, C., Zhu, X., Smith, M. A., & Perry, G. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.10.006 · Cited by 734 · see citing works
Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model
Du, H., Guo, L., Yan, S., Sosunov, A. A., McKhann, G. M., & ShiDu Yan, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006586107 · Cited by 704 · see citing works
Mitochondrial dysfunction in Parkinson's disease
Winklhofer, K. F., & Haass, C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.08.013 · Cited by 688 · cited 1× · see citing works
“, Huntington’s disease [39], amyotrophic lateral sclerosis [40], Parkinson’s disease [41], Friedreich ataxia [42], Alzheimer’s disease [43]), and chronic liver diseases (e.”
BackgroundMitochondrial dynamics in type 2 diabetes: Pathophysiological implications
Rovira-Llopis, S., Bañuls, C., Diaz-Morales, N., Hernandez-Mijares, A., Rocha, M., & Victor, V. M. (2017) · Redox Biology · doi:10.1016/j.redox.2017.01.013 · Cited by 657 · cited 1× · see citing works
“OPA-1 is responsible for fusion of the inner membrane and upkeep of mitochondrial cristae structure [96].”
BackgroundCalkins, M. J., Manczak, M., Mao, P., Shirendeb, U., & Reddy, P. H. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr381 · Cited by 646 · cited 2× · see citing works
“This also contributes to dysfunctional mitochondrial transport, increased hyperphosphorylation of tau, and synaptic dysfunction [75].”
BackgroundSelf-citationMechanisms of Selective Autophagy
Zaffagnini, G., & Martens, S. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.02.004 · Cited by 591 · cited 6× · see citing works
“The cargo receptor proteins recognize poly-ubiquitin chains on the surface of the targeted cargo, which triggers selective autophagy [83].”
BackgroundInfluentialBasal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand
McWilliams, T. G., Prescott, A. R., Montava-Garriga, L., Ball, G., Singh, F., Barini, E., Muqit, M. M. K., Brooks, S. P., & Ganley, I. G. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.008 · Cited by 591 · cited 2× · see citing works
“mitophagy was able to occur without the presence of PINK1 [87].”
BackgroundSzeto, H. H. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12461 · Cited by 550 · cited 2× · see citing works
“Furthermore, loss of phospholipids—particularly the cardiolipin of the IMM—exacerbates the pathology of AD [71].”
BackgroundMechanisms of Autophagosome Biogenesis
Rubinsztein, D. C., Shpilka, T., & Elazar, Z. (2012) · Current Biology · doi:10.1016/j.cub.2011.11.034 · Cited by 489 · cited 2× · see citing works
“The source of membrane for the phagophore is the Golgi apparatus, which assists with lipids and proteins for the phagophore to fully develop into an autophagosome [108].”
BackgroundA selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients
Maurer, I. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00112-3 · Cited by 475 · cited 2× · see citing works
“These research findings are congruent with the reduction in COX activity found in postmortem AD brains [70].”
BackgroundResultMitochondria-targeted antioxidants protect against amyloid-β toxicity in Alzheimer's disease neurons
Manczak, M., Mao, P., Calkins, M. J., Cornea, A., Reddy, A. P., Murphy, M. P., Szeto, H. H., Park, B., & Reddy, P. H. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100564 · Cited by 469 · see citing works
Self-citationMańczak, M., & Reddy, P. H. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds072 · Cited by 453 · cited 2× · see citing works
“On the basis of these findings, they concluded that Drp1 interacts with Aβ and P-Tau, likely leading to excessive mitochondrial fragmentation and mitochondrial and synaptic deficiencies, ultimately possibly leading to neuronal damage and cognitive decline [72].”
BackgroundSelf-citationMontine, T. J., Neely, M. D., Quinn, J. F., Beal, M. F., Markesbery, W. R., Roberts, L. J., & Morrow, J. D. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00807-9 · Cited by 449 · see citing works
Amyloid toxicity in Alzheimer’s disease
Reiss, A. B., Arain, H. A., Stecker, M. M., Siegart, N. M., & Kasselman, L. J. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0063 · Cited by 447 · cited 1× · see citing works
“AD has had a major impact on the global economy, costing $800 billion in 2015 [3].”
BackgroundAutophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications
Uddin, M. S., Stachowiak, A., Mamun, A. A., Tzvetkov, N. T., Takeda, S., Atanasov, A. G., Bergantin, L. B., Abdel‐Daim, M. M., & Stankiewicz, A. M. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00004 · Cited by 440 · cited 1× · see citing works
“amyloid-beta protein to a disease-causing conformation, phosphorylated tau damage, and resultant cellular and mitochondrial damage [49,50].”
BackgroundReddy, P. H., Tripathi, R., Troung, Q., Tirumala, K., Reddy, T. P., Anekonda, V., Shirendeb, U. P., Calkins, M. J., Reddy, A. P., Mao, P., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.011 · Cited by 394 · see citing works
Self-citationNuclear DNA damage signalling to mitochondria in ageing
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.14 · Cited by 387 · cited 3× · see citing works
“This results in a limitation to biogenesis, and mitochondrial DNA damage with age, which further exacerbates mitophagy dysfunction [117].”
BackgroundInfluentialOxidative phosphorylation versus glycolysis: what fuel do spermatozoa use?
du Plessis, S. S., Agarwal, A. K., Mohanty, G., & van der Linde, M. (2014) · Asian Journal of Andrology · doi:10.4103/1008-682x.135123 · Cited by 384 · cited 1× · see citing works
“In the cytoplasm of the cell, a molecule of glucose is broken down and phosphorylated to two molecules of glyceraldehyde-3-phosphate, which through a series of phosphorylation, dephosphorylation, and dehydration events are converted to two molecules of pyruvate [24,25].”
BackgroundMitochondria and Ischemia/Reperfusion Injury
Honda, H. M., Kôrge, P., & Weiss, J. N. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1341.022 · Cited by 377 · cited 1× · see citing works
“, ischemic reperfusion [36], cardiomyopathy [37], congenital heart diseases [38]), neurodegenerative diseases (e.”
BackgroundLetts, J. A., & Sazanov, L. A. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3460 · Cited by 376 · cited 10× · see citing works
“Complexes I, II, IV, and V are transmembrane proteins fitted within the IMM [28].”
BackgroundInfluentialProtective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease
Reddy, P. H., Manczak, M., Yin, X., Grady, M. C., Mitchell, A., Tonk, S., Kuruva, C. S., Bhatti, J. S., Kandimalla, R., Vijayan, M., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170512 · Cited by 354 · cited 5× · see citing works
“The mitochondria themselves tend to be greater in number and smaller in size due to excessive mitochondrial fragmentation, especially in the presence of Aβ and P-Tau [2,4,7,14,15].”
BackgroundInfluentialSelf-citationBasal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
Lee, J. J., Sánchez-Martínez, Á., Martinez, A., Benincá, C., Mayor, U., Clague, M. J., & Whitworth, A. J. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201801044 · Cited by 343 · cited 2× · see citing works
“Compared to stress-induced mitophagy, basal mitophagy is governed independent of PINK1, and likely parkin as well [87,88].”
BackgroundCardiolipin and mitochondrial cristae organization
Ikon, N., & Ryan, R. O. (2017) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2017.03.013 · Cited by 338 · cited 2× · see citing works
“These deep folds project almost diagonal to one another, and tightly pack a large IMM with an expansive surface area, allowing multiple successions of complexes along the membrane to conduct electron transport and oxidative phosphorylation [31,32].”
BackgroundProgrammed mitophagy is essential for the glycolytic switch during cell differentiation
Esteban‐Martínez, L., Sierra‐Filardi, E., McGreal, R., Salazar‐Roa, M., Mariño, G., Seco, E., Durand, S., Enot, D. P., Graña‐Castro, O., Malumbres, M., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201695916 · Cited by 333 · cited 3× · see citing works
“In this example, in order for differentiation to occur, Atg5 and NIX proteins usher mitochondria along the mitophagy pathway [93].”
BackgroundInfluentialCai, Q., Zakaria, H. M., Simone, A., & Sheng, Z. (2012) · Current Biology · doi:10.1016/j.cub.2012.02.005 · Cited by 332 · cited 3× · see citing works
“Their study controlled for parkin-mediated mitophagy by eliminating parkin, and noted the slower rates of mitophagy of depolarized (dysfunctional) mitochondria [112].”
InfluentialReddy, P. H., McWeeney, S. K., Park, B. S., Mańczak, M., Gutala, R. V., Partovi, D., Jung, Y., Yau, V., Searles, R. P., Mori, M., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh140 · Cited by 327 · cited 2× · see citing works
“Using global microarray analysis, Reddy and colleagues [52] measured mRNA levels in transgenic APP (amyloid precursor protein) mice at three different ages: 2-, 5-, and 18-months.”
BackgroundSelf-citationMolecular Mechanisms of Mitochondrial Autophagy/Mitophagy in the Heart
Saito, T., & Sadoshima, J. (2015) · Circulation Research · doi:10.1161/circresaha.116.303790 · Cited by 321 · cited 2× · see citing works
“MIRO is a mitochondrial OMM protein [107].”
BackgroundParkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells
Villa, E., Proïcs, E., Rubio‐Patiño, C., Obba, S., Zunino, B., Bossowski, J. P., Rozier, R., Chiche, J., Mondragón, L., Riley, J. S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.087 · Cited by 315 · cited 2× · see citing works
“Ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1) is an E3 ubiquitin protein ligase that targets proteins for autophagy via ubiquitination [103].”
BackgroundHow do delays in treatment affect patient prognosis in head and neck cancer?
Mohamedbhai, H., Thomas, S., Ali, S. R., Whitley, S., Liew, C., Sadiq, Z., Kalavrezos, N., & Hutchinson, I. (2017) · British Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.bjoms.2017.08.058 · Cited by 303 · cited 3× · see citing works
“A proteasome is a complex of proteases, which are enzymes with active sites oriented to denature and degrade proteins, specifically marked for degradation by ubiquitination (Figure 5) [106].”
BackgroundInfluentialMolecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications
Apostolova, N., & Víctor, V. M. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.5952 · Cited by 303 · cited 3× · see citing works
“Superoxide dismutase in mitochondria rapidly converts O2− to H2O2, another less-damaging ROS, via the dismutation redox reaction [33–35].”
BackgroundMitochondria in Huntington's disease
Damiano, M. G., Galvan, L., Déglon, N., & Brouillet, E. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.07.012 · Cited by 282 · cited 1× · see citing works
“, Huntington’s disease [39], amyotrophic lateral sclerosis [40], Parkinson’s disease [41], Friedreich ataxia [42], Alzheimer’s disease [43]), and chronic liver diseases (e.”
BackgroundThe role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease
Wang, X., Su, B., Zheng, L., Perry, G. L., Smith, M. A., & Zhu, X. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05867.x · Cited by 278 · see citing works
Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer's disease patient brains
Ye, X., Sun, X., Starovoytov, V., & Cai, Q. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv056 · Cited by 274 · cited 1× · see citing works
“During autophagy, both Mfn1 and Mfn2 depend on Gp78 for ubiquitination and subsequent degradation [62].”
BackgroundMitochondrial Aspects of Synaptic Dysfunction in Alzheimer’s Disease
Cai, Q., & Tammineni, P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160726 · Cited by 274 · see citing works
Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease
Reddy, P. H. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.03.042 · Cited by 264 · see citing works
Self-citationFranco, L. H., Nair, V. R., Scharn, C. R., Xavier, R. J., Torrealba, J. R., Shiloh, M. U., & Levine, B. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.11.002 · Cited by 253 · cited 1× · see citing works
“The Smad ubiquitin regulatory factor 1 (SMURF1) protein is an E3 ubiquitin ligase that plays the essential role of mediating the ubiquitination of target substrates for proteases to break down during autophagy [104].”
BackgroundPearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA.
McShane, M. A., Hammans, S. R., Sweeney, M. G., et al. (1991) · PubMed · Cited by 252 · see citing works
Abnormal Mitochondrial Dynamics in the Pathogenesis of Alzheimer's Disease
Zhu, X., Perry, G., Smith, M. A., & Wang, X. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-129005 · Cited by 242 · see citing works
Quinsay, M. N., Thomas, R. L., Lee, Y., & Gustafsson, Å. B. (2010) · Autophagy · doi:10.4161/auto.6.7.13005 · Cited by 239 · cited 8× · see citing works
“The initial response to mitochondrial dysfunction would be selective autophagy of damaged mitochondria, which is called mitophagy [82].”
BackgroundInfluentialThe Association of Tau With Mitochondrial Dysfunction in Alzheimer’s Disease
Cheng, Y., & Bai, F. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00163 · Cited by 239 · see citing works
Selective and Non-Selective Autophagic Degradation of Mitochondria in Yeast
Bhatia‐Kiššová, I., Salin, B., Schaëffer, J., Bhatia, S., Manon, S., & Camougrand, N. M. (2007) · Autophagy · doi:10.4161/auto.4034 · Cited by 223 · cited 5× · see citing works
“In macro-autophagy, also known as “non-selective autop ”, a double-membraned vesicle called an autophagosome engulfs its target by sequestering some portion of the cytoplasm, including co tents such as organel es (Figure 3) [79,81,82].”
BackgroundInfluentialHollville, É., Carroll, R. G., Cullen, S. P., & Martin, S. J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.06.001 · Cited by 221 · cited 3× · see citing works
“The pro-apoptotic Bcl-2 family of proteins also begin to outnumber the anti-apoptotic Bcl-2 proteins, and the mitochondrial membrane integrity begins to wane and increase in permeability, becoming more polarized [90].”
BackgroundInfluentialAlterations in Mitochondrial Quality Control in Alzheimer’s Disease
Cai, Q., & Tammineni, P. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00024 · Cited by 215 · cited 10× · see citing works
“Factors such as oxidative damage, cytochrome c leakage from the IMM, Ca2+ release, loss of membrane potential, caspase activation, and mtDNA damage are signs of mitochondrial dysfunction, and precede selective autophagy [2,13,76,116].”
BackgroundInfluentialMutations in Fis1 disrupt orderly disposal of defective mitochondria
Shen, Q., Yamano, K., Head, B. P., Kawajiri, S., Cheung, J. T. M., Wang, C., Cho, J.-H., Hattori, N., Youle, R. J., & van der Bliek, A. M. (2014) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-09-0525 · Cited by 209 · cited 4× · see citing works
“Under stressed conditions, Fis1 contributes to the fission of mitochondria which are en-route to mitophagy (Figure 5) [95].”
BackgroundInfluentialRegulation of mitophagy by the Gp78 E3 ubiquitin ligase
Fu, M., St-Pierre, P., Shankar, J., Wang, P. T. C., Joshi, B., & Nabi, I. R. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-08-0607 · Cited by 204 · cited 5× · see citing works
“Upon loss of mitochondrial membrane potential, Gp78 is activated to initiate mitophagy and attract enhanced green fluorescent protein (EGFP)-LC3-1—an autophagosome marker—to the mitochondria-associated ER [105].”
BackgroundInfluentialMańczak, M., Jung, Y., Park, B. S., Partovi, D., & Reddy, P. H. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02884.x · Cited by 192 · cited 1× · see citing works
“This leads the surface receptor protein PINK1 to change to its stable conformation and bind to the OMM [54].”
BackgroundSelf-citationLin, M.-Y., Cheng, X., Tammineni, P., Xie, Y., Zhou, B., Cai, Q., & Sheng, Z. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.004 · Cited by 183 · see citing works
Kandimalla, R. J. L., Mańczak, M., Fry, D., Yeguvapalli, S., Sesaki, H., & Reddy, P. H. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw312 · Cited by 180 · cited 3× · see citing works
“Neuronal mitochondria’s lifespan assists in the worsening of AD pathology when combined with the impediments to mitophagy [2,78].”
BackgroundSelf-citationMańczak, M., Kandimalla, R. J. L., Fry, D., Sesaki, H., & Reddy, P. H. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw330 · Cited by 179 · cited 2× · see citing works
“These findings suggest that a partial reduction of Drp1 is protective against Aβ-induced toxicities in APP mice [77].”
BackgroundSelf-citationMańczak, M., Kandimalla, R. J. L., Yin, X., & Reddy, P. H. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy335 · Cited by 170 · see citing works
Self-citationTammineni, P., Ye, X., Feng, T., Aikal, D., & Cai, Q. (2017) · eLife · doi:10.7554/elife.21776 · Cited by 169 · cited 2× · see citing works
“(2017), they studied Aβ peptides and Aβ oligomers (AβOs) in mutant hAPP mice and AD patient cells, and it was found that AβOs interacted with autophagic vacuoles in the distal axons of mutant mouse cells [113].”
BackgroundRelationship between Exercise and Alzheimer’s Disease: A Narrative Literature Review
Meng, Q., Lin, M.-S., & Tzeng, I.-S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00131 · Cited by 158 · see citing works
Santos, R. X., Correia, S., Wang, X.-L., Perry, G., Smith, M. A., Moreira, P., & Zhu, X.-W. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100666 · Cited by 157 · see citing works
Small molecules as therapeutic drugs for Alzheimer's disease
Oliver, D., & Reddy, P. H. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.03.001 · Cited by 156 · cited 6× · see citing works
“Factors such as oxidative damage, cytochrome c leakage from the IMM, Ca2+ release, loss of membrane potential, caspase activation, and mtDNA damage are signs of mitochondrial dysfunction, and precede selective autophagy [2,13,76,116].”
BackgroundInfluentialSelf-citationLi, J., Qi, W. D., Chen, G., Feng, D., Liu, J., Ma, B., Zhou, C., Mu, C., Zhang, W., Chen, Q., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1017180 · Cited by 154 · cited 1× · see citing works
“Mitochondrial E3 ubiquitin protein ligase 1 is an E3 ubiquitin protein ligase that mediates ATG5and ULK1-dependent mitophagy initiated by selenite [102].”
BackgroundReddy, P. H. (2006) · BioMed Research International · doi:10.1155/jbb/2006/31372 · Cited by 153 · cited 1× · see citing works
“The disease is believed to originate with neuronal degeneration in the second layer of the entorhinal cortex, and progresses to the hippocampus, temporal cortex, front-parietal cortex, and further to the subcortical nuclei [4,8].”
BackgroundSelf-citationMitophagy links oxidative stress conditions and neurodegenerative diseases
Jung, J., Huh, Y., Shefa, U., Jeong, N., Song, I., Chung, H.-J., & Kim, D. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.249218 · Cited by 152 · cited 7× · see citing works
“However, there is mitophagic dysfunction in AD [2,17].”
BackgroundInfluentialMitochondria in Amyotrophic Lateral Sclerosis: A Trigger and a Target
Dupuis, L., de Aguilar, J. G., Oudart, H., de Tapia, M., Barbeito, L., & Loeffler, J. (2004) · Neurodegenerative Diseases · doi:10.1159/000085063 · Cited by 150 · cited 1× · see citing works
“, Huntington’s disease [39], amyotrophic lateral sclerosis [40], Parkinson’s disease [41], Friedreich ataxia [42], Alzheimer’s disease [43]), and chronic liver diseases (e.”
BackgroundBhatti, G. K., Reddy, A. P., Reddy, P. H., & Bhatti, J. S. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00369 · Cited by 145 · see citing works
Self-citationMultiple faces of dynamin-related protein 1 and its role in Alzheimer's disease pathogenesis
Kandimalla, R. J. L., & Reddy, P. H. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.018 · Cited by 144 · cited 2× · see citing works
“Mitochondria may undergo fusion and increase in size, while reducing their numbers; or undergo fission and reduce their size, while increasing in number [6,76,115].”
BackgroundSelf-citationAmyloid β-42 induces neuronal apoptosis by targeting mitochondria
Han, X., Hu, Y., Yang, Z., Jiang, L., Shi, S.-L., Li, Y.-R., Guo, M., Wu, H., & Wan, Y. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7203 · Cited by 144 · cited 5× · see citing works
“OPA1 OPA-1 is responsible for fusion of the inner membrane and upkeep of mitochondrial cristae structure [96].”
BackgroundInfluentialMitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation
Yang, L., Youngblood, H. A., Wu, C., & Zhang, Q. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00197-z · Cited by 143 · see citing works
Measurement of Mitochondrial NADH and FAD Autofluorescence in Live Cells
Bartolomé, F. B., & Abramov, A. Y. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2257-4_23 · Cited by 131 · cited 10× · see citing works
“Complex II is peripheral to the IMM, oxidizes FADH2 to FAD, and complex III pumps protons across the IMM into the intermembrane space [28,29].”
BackgroundInfluentialYan, S. D., & Stern, D. M. (2005) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2005.00427.x · Cited by 131 · cited 2× · see citing works
“Yan and Stern also demonstrated that Aβ interaction with cyclophilin D is responsible for the interference with IMM complexes and reduction in ATP production [69].”
Backgroundvan Weelden, S. W. H., van Hellemond, J. J., Opperdoes, F. R., & Tielens, A. G. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412447200 · Cited by 123 · cited 4× · see citing works
“Through the process of the Krebs cycle, which occurs in the mitochondrial matrix, mitochondria reduce FAD (oxidized form of FADH2) to FADH2 (flavin adenine dinucleotide) and NAD+ to NADH, and the energy needed to drive the electron transport chain (ETC) is stored in the body energy of nitrogen bound to hydrogen in FAD…”
BackgroundInfluentialLysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain
Zhang, Y., Bharathi, S. S., Rardin, M. J., Lu, J. L., Maringer, K. V., Sims‐Lucas, S., Prochownik, E. V., Gibson, B. W., & Goetzman, E. S. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.785022 · Cited by 121 · cited 1× · see citing works
“The IMM does however have cardiolipin—a phospholipid which is targeted and bound by lysine desuccinylase SIRT5, enabling its function [30].”
BackgroundMolecular Basis of Alzheimer’s Disease: Focus on Mitochondria
Oliver, D. M. A., & Reddy, P. H. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190048 · Cited by 120 · cited 4× · see citing works
“Factors such as oxidative damage, cytochrome c leakage from the IMM, Ca2+ release, loss of membrane potential, caspase activation, and mtDNA damage are signs of mitochondrial dysfunction, and precede selective autophagy [2,13,76,116].”
BackgroundInfluentialSelf-citationSaneto, R. P., Cohen, B. H., Copeland, W. C., & Naviaux, R. K. (2013) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2012.09.014 · Cited by 116 · see citing works
Haslip, M., Dostanic, I., Huang, Y., Zhang, Y., Russell, K. S., Jurczak, M. J., Mannam, P., Giordano, F. J., ERZURUM, S. C., & Lee, P. J. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304865 · Cited by 115 · cited 1× · see citing works
“Mitochondrial uncoupling, including uncoupling proteins like UCP2, induce the PINK1–parkin activities of stress-induced mitophagy [86,89].”
BackgroundMitochondrial hepatopathies: Advances in genetics and pathogenesis
Lee, W. S., & Sokol, R. J. (2007) · Hepatology · doi:10.1002/hep.21710 · Cited by 113 · cited 1× · see citing works
“, Pearson’s syndrome [44], villus atrophy syndrome [45], neonatal liver failure [46], Alpers–Huttenlocher syndrome [47]).”
BackgroundKaramanlidis, G., Bautista‐Hernández, V., Fynn‐Thompson, F., del Nido, P. J., & Tian, R. (2011) · Circulation Heart Failure · doi:10.1161/circheartfailure.111.961474 · Cited by 112 · cited 1× · see citing works
“, ischemic reperfusion [36], cardiomyopathy [37], congenital heart diseases [38]), neurodegenerative diseases (e.”
BackgroundLiver Disease in Mitochondrial Disorders
Lee, W. S., & Sokol, R. J. (2007) · Seminars in Liver Disease · doi:10.1055/s-2007-985071 · Cited by 105 · cited 1× · see citing works
“, Pearson’s syndrome [44], villus atrophy syndrome [45], neonatal liver failure [46], Alpers–Huttenlocher syndrome [47]).”
BackgroundMitochondria and Heart Disease
Griffiths, E. J. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2869-1_11 · Cited by 90 · cited 1× · see citing works
“, ischemic reperfusion [36], cardiomyopathy [37], congenital heart diseases [38]), neurodegenerative diseases (e.”
BackgroundAβ1-42 monomers or oligomers have different effects on autophagy and apoptosis
Guglielmotto, M., Monteleone, D., Piras, A., Valsecchi, V., Tropiano, M., Ariano, S., Fornaro, M., Vercelli, A., Puyal, J., Arancio, O., et al. (2014) · Autophagy · doi:10.4161/auto.30001 · Cited by 87 · cited 2× · see citing works
“(2014) attested that intracellular Aβ monomers, rather than oligomers, impacted autophagy to a greater extent [114].”
BackgroundMicroRNAs, Aging, Cellular Senescence, and Alzheimer's Disease
Reddy, P. H., Williams, J. M., Smith, F., Bhatti, J. S., Kumar, S., Vijayan, M., Kandimalla, R. J. L., Kuruva, C. S., Wang, R., Mańczak, M., et al. (2017) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2016.12.009 · Cited by 87 · see citing works
Self-citationSzeto, H. H., & Liu, S. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.10.013 · Cited by 87 · cited 2× · see citing works
“These deep folds project almost diagonal to one another, and tightly pack a large IMM with an expansive surface area, allowing multiple successions of complexes along the membrane to conduct electron transport and oxidative phosphorylation [31,32].”
BackgroundEiyama, A., Kondo‐Okamoto, N., & Okamoto, K. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.04.030 · Cited by 68 · cited 9× · see citing works
“As in other forms of mitophagy, stress-induced mitophagy manages the quality and quantity of mitochondria within the cell, though specifically responding to starvation [80].”
BackgroundInfluentialMitochondrial DNA polymorphisms specifically modify cerebral β-amyloid proteostasis
Scheffler, K., Krohn, M., Dunkelmann, T., Stenzel, J., Miroux, B., Ibrahim, S. M., Halbach, O. V. B. U., Heinze, H., Walker, L. C., Gsponer, J. A., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0980-x · Cited by 61 · cited 2× · see citing works
“found that in AD cells in vivo, Aβ deposition is strongly correlated with mitochondrial-DNA-damaging polymorphisms [68].”
BackgroundRegulation of glycolysis in brown adipocytes by HIF-1α
Basse, A. L., Isidor, M. S., Winther, S., Skjoldborg, N. B., Murholm, M., Andersen, E. S., Pedersen, S. B., Wolfrum, C., Quistorff, B., & Hansen, J. B. (2017) · Scientific Reports · doi:10.1038/s41598-017-04246-y · Cited by 54 · cited 1× · see citing works
“In the cytoplasm of the cell, a molecule of glucose is broken down and phosphorylated to two molecules of glyceraldehyde-3-phosphate, which through a series of phosphorylation, dephosphorylation, and dehydration events are converted to two molecules of pyruvate [24,25].”
BackgroundTammineni, P., Jeong, Y. Y., Feng, T., Aikal, D., & Cai, Q. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx321 · Cited by 51 · see citing works
Friedreich’s ataxia is a mitochondrial disorder
Kaplan, J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.10948 · Cited by 37 · cited 1× · see citing works
“, Huntington’s disease [39], amyotrophic lateral sclerosis [40], Parkinson’s disease [41], Friedreich ataxia [42], Alzheimer’s disease [43]), and chronic liver diseases (e.”
BackgroundSykes, S. E., & Hajduk, S. L. (2012) · Eukaryotic Cell · doi:10.1128/ec.00269-12 · Cited by 36 · cited 4× · see citing works
“Through the process of the Krebs cycle, which occurs in the mitochondrial matrix, mitochondria reduce FAD (oxidized form of FADH2) to FADH2 (flavin adenine dinucleotide) and NAD+ to NADH, and the energy needed to drive the electron transport chain (ETC) is stored in the body energy of nitrogen bound to hydrogen in FAD…”
BackgroundInfluentialMitochondria shape cardiac metabolism
Gottlieb, R. A., & Bernstein, D. (2015) · Science · doi:10.1126/science.aad8222 · Cited by 35 · cited 1× · see citing works
“During the maturation of cardiomyocytes, mitochondria which primarily use glucose for ATP are replaced using with mitochondria which preferentially use fatty acids through programmed mitophagy [94].”
BackgroundBonda, D., Smith, M. A., Perry, G. L., Lee, H., Wang, X., & Zhu, X. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798072562 · Cited by 34 · cited 2× · see citing works
“In AD, mitochondrial dynamics are believed to be upset by the phosphorylation of tau proteins, which are structural components of microtubules, or interaction with amyloid beta polypeptides, which amalgamate extracellularly and traverse membranes to interact with mitochondria [22,23].”
BackgroundLi, Y., Lu, J. N., Cao, X., Zhao, H., Gao, L., Xia, P., & Pei, G. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/7698560 · Cited by 29 · see citing works
Lim, K., & Joo, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093398 · Cited by 28 · see citing works
Cai, Z., Xu, J., Xue, S.-R., Liu, Y.-Y., Zhang, Y., Zhang, X.-Z., Wang, X., Wu, F., & Li, X. (2015) · Neural Regeneration Research · doi:10.4103/1673-5374.162763 · Cited by 15 · cited 2× · see citing works
“Seven in absentia homolog 1 (SIAH1) regulates the α-synuclein monoubiquitination, and induces α-synuclein accumulation and intracellular inclusion formation [101].”
Background
Flagged first, then by citations
2 of the 127 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Lilienbaum, 2013, Relationship between the proteasomal system and autophagy, Int. J. Biochem. Mol. Biol., 4, 1
Cited by
Sorted by citations
Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
Xu, X., Pang, Y., & Fan, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02253-4 · Cited by 939 · see citing works
Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease
Misrani, A., Tabassum, S., & Yang, L. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.617588 · Cited by 654 · see citing works
Mitochondria in health, disease, and aging
Harrington, J. S., Ryter, S. W., Plataki, M. E., Price, D. R., & Choi, A. M. K. (2023) · Physiological Reviews · doi:10.1152/physrev.00058.2021 · Cited by 622 · see citing works
Gómez-Virgilio, L., Silva-Lucero, M.-D.-C., Flores-Morelos, D.-S., Gallardo-Nieto, J., Lopez-Toledo, G., Abarca-Fernandez, A.-M., Zacapala-Gómez, A.-E., Luna-Muñoz, J., Montiel-Sosa, F., Soto-Rojas, L. O., et al. (2022) · Cells · doi:10.3390/cells11152262 · Cited by 431 · see citing works
PINK1/Parkin-mediated mitophagy in neurodegenerative diseases
Li, J., Yang, D., Li, Z., Zhao, M., Wang, D., Sun, Z., Wen, P., Dai, Y., Gou, F., Ji, Y., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101817 · Cited by 388 · see citing works
Defective mitophagy in Alzheimer’s disease
Pradeepkiran, J. A., & Reddy, P. H. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101191 · Cited by 367 · see citing works
“Mitochondria are in a dynamic state in the cells (Reddy and Oliver, 2019).”
BackgroundInfluentialSelf-citationAmyloid Beta in Aging and Alzheimer’s Disease
Sehar, U., Rawat, P., Reddy, A. P., Kopel, J. J., & Reddy, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112924 · Cited by 385 · see citing works
Self-citationOxidative Stress: Signaling Pathways, Biological Functions, and Disease
Liu, S., Liu, J., Wang, Y., Deng, F., & Deng, Z. (2025) · MedComm · doi:10.1002/mco2.70268 · Cited by 435 · see citing works
Synaptic basis of Alzheimer’s disease: Focus on synaptic amyloid beta, P-tau and mitochondria
John, A., & Reddy, P. H. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101208 · Cited by 359 · see citing works
“Lead) (George and Reddy, 2019).”
BackgroundInfluentialSelf-citationThe biological pathways of Alzheimer disease: a review
Calabrò, M., Rinaldi, C., Santoro, G., & Crisafulli, C. (2020) · AIMS neuroscience · doi:10.3934/neuroscience.2021005 · Cited by 271 · see citing works
“In AD, high levels of Aβ and Tau inhibit the expression of PINK1 and parkin, thereby reducing the number of autophagosomes leading to increased dysfunctional lysosomes and the severe disease pathology [312,314].”
BackgroundRole of AMPK mediated pathways in autophagy and aging
Ge, Y., Zhou, M., Chen, C., Wu, X., & Wang, X. (2021) · Biochimie · doi:10.1016/j.biochi.2021.11.008 · Cited by 253 · see citing works
The Role of NLRP3 Inflammasome in Alzheimer’s Disease and Potential Therapeutic Targets
Liang, T., Zhang, Y., Wu, S., Chen, Q., & Wang, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.845185 · Cited by 220 · see citing works
Bustamante-Barrientos, F. A., Luque‐Campos, N., Araya, M. J., Lara-Barba, E., Solminihac, J. D., Pradenas, C., Molina, L., Herrera-Luna, Y., Utreras‐Mendoza, Y., Elizondo-Vega, R. J., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04493-w · Cited by 194 · see citing works
Magnesium Is a Key Player in Neuronal Maturation and Neuropathology
Yamanaka, R., Shindo, Y., & Oka, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143439 · Cited by 179 · see citing works
Morton, H., Kshirsagar, S., Orlov, E., Bunquin, L. E., Sawant, N. A., Boleng, L., George, M., Basu, T., Ramasubramanian, B., Pradeepkiran, J. A., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.07.013 · Cited by 171 · see citing works
Self-citationDynamics of Dynamin-Related Protein 1 in Alzheimer’s Disease and Other Neurodegenerative Diseases
Oliver, D., & Reddy, P. H. (2019) · Cells · doi:10.3390/cells8090961 · Cited by 169 · see citing works
Self-citationPeng, Y., Jin, H., Xue, Y.-H., Chen, Q., Yao, S., Du, M., & Liu, S. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1206572 · Cited by 176 · see citing works
Deregulated mitochondrial microRNAs in Alzheimer's disease: Focus on synapse and mitochondria
Gowda, P., Reddy, P. H., & Kumar, S. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101529 · Cited by 166 · see citing works
Self-citationDefective Autophagy and Mitophagy in Aging and Alzheimer’s Disease
Tran, M. K., & Reddy, P. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.612757 · Cited by 152 · see citing works
“In AD, accumulation of Aβ into oligomers and fibrils is implicated as one of the early events in AD development and progression (Reddy, 2006; Reddy and Oliver, 2019; Murphy and Levine, 2010; Hamley, 2012).”
BackgroundInfluentialSelf-citationRelationship between Exercise and Alzheimer’s Disease: A Narrative Literature Review
Meng, Q., Lin, M.-S., & Tzeng, I.-S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00131 · Cited by 158 · see citing works
“Keywords: Alzheimer’s disease, neurogenesis, cognitive function, exercise, hippocampal volume BACKGROUND Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and multiple cognitive disorders (Reddy and Oliver, 2019).”
BackgroundAlzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia
Eshraghi, M., Adlimoghaddam, A., Mahmoodzadeh, A., Sharifzad, F., Yasavoli-Sharahi, H., Lorzadeh, S., Albensi, B. C., & Ghavami, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073330 · Cited by 158 · see citing works
“, through mitophagy) is severely compromised in AD [114,135].”
BackgroundCheng, G., Kwong, C. H. T., Wang, Q., Kam, H., Xie, B., Lee, S. M., Chen, G., & Wang, R. (2023) · ACS Nano · doi:10.1021/acsnano.3c00041 · Cited by 150 · see citing works
Bhatti, G. K., Reddy, A. P., Reddy, P. H., & Bhatti, J. S. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00369 · Cited by 145 · see citing works
“Reddy and Oliver (2019) recently demonstrated that the accumulation of Aβ and phosphorylated tau induces defective autophagy and mitophagy in AD.”
BackgroundSelf-citationMitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation
Yang, L., Youngblood, H. A., Wu, C., & Zhang, Q. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00197-z · Cited by 143 · see citing works
Jurcău, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111847 · Cited by 150 · see citing works
Insulin Resistance at the Crossroad of Alzheimer Disease Pathology: A Review
Berlanga‐Acosta, J., Guillén, G. E., Rodríguez-Rodríguez, N., Bringas-Vega, M. L., García-del-Barco-Herrera, D., Berlanga-Saez, J. O., Ojalvo, A. G., Valdés-Sosa, M. J., & Valdes-Sosa, P. A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.560375 · Cited by 139 · see citing works
“Thus, a reduction in the rates of mitophagy is an age hallmark and an AD badge, when it is associated with Aβ and hyperphosphorylated Tau (257).”
BackgroundRelationships between Mitochondrial Dysfunction and Neurotransmission Failure in Alzheimer’s Disease
Wong, K. Y., Roy, J., Fung, M., Heng, B. C., Zhang, C., & Lim, L. W. (2020) · Aging and Disease · doi:10.14336/ad.2019.1125 · Cited by 119 · see citing works
“Generally, initiation of the mitophagy pathway occurs via the relocation of cardiolipin, a diphosphatidylglycerol lipid, from the inner mitochondrial membrane to outer mitochondrial membrane [23].”
BackgroundInfluentialHamano, T., Enomoto, S., Shirafuji, N., Ikawa, M., Yamamura, O., Yen, S.-H. C., & Nakamoto, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147475 · Cited by 114 · see citing works
MicroRNAs: pioneering regulators in Alzheimer’s disease pathogenesis, diagnosis, and therapy
Li, Y.-B., Fu, Q., Guo, M., Du, Y., Chen, Y., & Cheng, Y. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03075-8 · Cited by 123 · see citing works
Wang, Z., Liu, J., Zhu, Z., Su, C.-F., Sreenivasmurthy, S. G., Iyaswamy, A., Lu, J., Chen, G., Song, J., & Li, M. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110968 · Cited by 108 · see citing works
Fišar, Z. (2022) · Biomolecules · doi:10.3390/biom12111676 · Cited by 110 · see citing works
Natural Compounds and Autophagy: Allies Against Neurodegeneration
Stacchiotti, A., & Corsetti, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.555409 · Cited by 105 · see citing works
“Recently, Reddy and Oliver (2019) reported reduced autophagy and mitophagy caused by excessive amyloidosis and tau deposition in AD.”
BackgroundMitophagy regulates integrity of mitochondria at synapses and is critical for synaptic maintenance
Han, S., Jeong, Y. Y., Sheshadri, P., Su, X. Y., & Cai, Q. (2020) · EMBO Reports · doi:10.15252/embr.201949801 · Cited by 92 · see citing works
“Importantly, the earliest features of the onset of the highly prevalent Alzheimer’s disease (AD) have been linked to mitochondrial pathology — abnormal accumulation of damaged mitochondria (Gibson & Shi, 2010; Swerdlow et al , 2010; Cai & Tammineni, 2016; Reddy & Oliver, 2019).”
Gouveia, F., Camins, A., Ettcheto, M., Bicker, J., Falcão, A. C., Cruz, M. T., & Fortuna, A. C. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101612 · Cited by 96 · see citing works
Neuron-astrocyte transmitophagy is altered in Alzheimer's disease
Lampinen, R., Belaya, I., Saveleva, L., Liddell, J. R., Rait, D., Huuskonen, M. T., Giniatullina, R., Sorvari, A., Soppela, L., Mikhailov, N., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105753 · Cited by 97 · see citing works
“Impairments in mitochondrial quality control have previously been linked to AD (Lampinen et al., 2018; Reddy and Oliver, 2019) and ADaffected neurons have previously been reported to accumulate dysfunctional mitochondria (Fang et al., 2019).”
BackgroundQuan, S., Fu, X., Cai, H., Ren, Z., Xu, Y., & Jia, L. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00815-2 · Cited by 107 · see citing works
“Specifically, numerous adverse factors, including elevated levels of pathogenic proteins in AD, could desta-bilize the neuronal mitochondrial genome [112, 113], leading to mitochondrial dysfunction, ultimately triggering the release of disrupted mtDNA into the extramito-chondrial space to initiate…”
Naeem, A., Prakash, R., Kumari, N., Ali Khan, M., Quaiyoom Khan, A., Uddin, S., Verma, S., AB Robertson, A., Boltze, J., & Shadab Raza, S. (2024) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2023.11.031 · Cited by 96 · see citing works
<scp>mTOR</scp> signaling and Alzheimer's disease: What we know and where we are?
Davoody, S., Asgari Taei, A., Khodabakhsh, P., & Dargahi, L. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14463 · Cited by 96 · see citing works
“97,98 mTORC1 regulates cell autophagy by recycling intracellular organelles through lysosomal degradation.”
BackgroundTorres, A. K., Jara, C., Olesen, M. A., & Tapia‐Rojas, C. (2021) · Scientific Reports · doi:10.1038/s41598-021-83910-w · Cited by 93 · see citing works
Exploring the bi‐directional relationship between autophagy and Alzheimer’s disease
Kuang, H., Tan, C., Tian, H., Liu, L., Yang, M.-W., Hong, F., & Yang, S. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13216 · Cited by 92 · see citing works
Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models
de la Cueva, M., Antequera, D., Ordóñez‐Gutiérrez, L., Wandosell, F. G., Camins, A., Carro, E., & Bartolomé, F. B. (2022) · Scientific Reports · doi:10.1038/s41598-022-13683-3 · Cited by 91 · see citing works
“Some works agree with our observations, also indicating that the Aβ peptide may be a trigger for mitophagy 13–18 , Our results show a dual effect of Aβ peptide overload.”
BackgroundAre mitophagy enhancers therapeutic targets for Alzheimer’s disease?
Pradeepkiran, J. A., Hindle, A., Kshirsagar, S., & Reddy, P. H. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112918 · Cited by 82 · see citing works
Self-citationLysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance
Lakpa, K. L., Khan, N., Afghah, Z., Chen, X., & Geiger, J. D. (2021) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-021-09990-7 · Cited by 77 · see citing works
“Furthermore, defective autophagy and mitophagy are present in AD (Reddy and Oliver 2019).”
BackgroundMeng, K., Jia, H., Hou, X., Zhu, Z., Lu, Y., Feng, Y., Feng, J., Xia, Y., Tan, R., Cui, F., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13020327 · Cited by 80 · see citing works
“It has been shown that mitophagy is impaired in the hippocampus of AD patients; thus, defective mitophagy leads to the accumulation of functionally defective mitochondria in the cell, which may be one of the main causes for the development of AD [36,54].”
Zhang, L., Fang, Y., Zhao, X., Zheng, Y., Ma, Y., Li, S., Huang, Z., & Li, L. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.02.010 · Cited by 78 · see citing works
“Studies have shown that many cellular changes are related to the development and progress of neurodegenerative diseases, including mitochondrial dysfunction, synaptic damage, hormonal imbalance, inflammatory responses, the formation and accumulation of hyperphosphorylated tau, and neuronal loss, among which mitochondr…”
BackgroundInfluentialZhao, N., Xia, J., & Xu, B. (2020) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2020.08.009 · Cited by 77 · see citing works
“J Sport Health Sc respiratory enzymes, ultrastructural deficits, including the loss of cristae, the development of vacuolar intramedullary lesions, and increased permeability, have been demonstrated in brain tissue in AD patients.5 Consequently, much evidence has been reported showing that excessive reactive oxygen sp…”
BackgroundInfluentialWang, X., Feng, S., Wang, Z., Chen, N., & Zhang, Y. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105433 · Cited by 76 · see citing works
Mitochondrial dysfunction, mitophagy, and role of dynamin‐related protein 1 in Alzheimer's disease
Medala, V. K., Gollapelli, B., Dewanjee, S., Ogunmokun, G., Kandimalla, R. J. L., & Vallamkondu, J. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24781 · Cited by 76 · see citing works
“Interestingly, some studies have shown no role of Drp1 in mitophagy (Li et al., 2019; Oliver & Reddy, 2019a; Reddy & Oliver, 2019).”
BackgroundProgrammed Death of Microglia in Alzheimer's Disease: Autophagy, Ferroptosis, and Pyroptosis
Qiu, Z., Zhang, H., Xia, M., Gu, J., Guo, K., Wang, H., & Miao, C. (2023) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2023.3 · Cited by 76 · see citing works
Spermidine, an autophagy inducer, as a therapeutic strategy in neurological disorders
Ghosh, I., Sankhe, R., Mudgal, J., Arora, D. S., & Nampoothiri, M. (2020) · Neuropeptides · doi:10.1016/j.npep.2020.102083 · Cited by 73 · see citing works
Yu, W., Jin, H., & Huang, Y. (2021) · Clinical Science · doi:10.1042/cs20200844 · Cited by 75 · see citing works
“In return, both enhanced A β deposit and NFTs can promote defective autophagy in AD [136].”
BackgroundD’Mello, S. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115911 · Cited by 77 · see citing works
Guha, S. K., Johnson, G. V. W., & Nehrke, K. W. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02084-0 · Cited by 71 · see citing works
Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets
Qian, S., Long, Y., Tan, G., Li, X., Xiang, B., Tao, Y., Xie, Z., & Zhang, X. (2024) · MedComm · doi:10.1002/mco2.70024 · Cited by 72 · see citing works
Role of mitochondria in physiological activities, diseases, and therapy
Wang, L., Zhou, X., & Lu, T. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00284-5 · Cited by 79 · see citing works
“Additionally, oligomeric Aβ and hyper-phosphorylated tau could interact with Drp1, inducing excessive mitochondrial fragmentation and ultimately contributing to neuronal damage and cognitive deficits in AD [112, 113].”
Transposable elements as new players in neurodegenerative diseases
Ravel‐Godreuil, C., Znaidi, R., Bonnifet, T., Joshi, R. L., & Fuchs, J. (2021) · FEBS Letters · doi:10.1002/1873-3468.14205 · Cited by 67 · see citing works
Li, H., Wei, T., Zhuang, M., Tan, C., Xie, T., Cai, J., Yao, Y., & Zhu, L. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01712-7 · Cited by 67 · see citing works
“Concurrently, ferritin overexpression reduced the number of SA-β -gal-positive cells (Fig.”
Swerdlow, N., & Wilkins, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249661 · Cited by 65 · see citing works
“AD mouse models have disrupted mitophagy[162].”
The Emerging Roles of Autophagy in Human Diseases
Lei, Y., & Klionsky, D. J. (2021) · Biomedicines · doi:10.3390/biomedicines9111651 · Cited by 66 · see citing works
Bhatti, J. S., Kaur, S., Mishra, J., HariKrishnaReddy, D., Singh, A., Reddy, A. P., Bhatti, G. K., & Reddy, P. H. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166798 · Cited by 66 · see citing works
Self-citationRoy, J., Wong, K. Y., Aquili, L., Uddin, M. S., Heng, B. C., Tipoe, G. L., Wong, K.-H., Fung, M., & Lim, L. W. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2022.100986 · Cited by 64 · see citing works
Dietary Mitophagy Enhancer: A Strategy for Healthy Brain Aging?
Varghese, N., Werner, S., Grimm, A., & Eckert, A. (2020) · Antioxidants · doi:10.3390/antiox9100932 · Cited by 66 · see citing works
Guo, J., Yang, G., He, Y., Xu, H., Fan, H., An, J., Zhang, L., Zhang, R., Cao, G., Hao, D., et al. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-01009-8 · Cited by 65 · see citing works
Zhang, Y., Miao, Y., Jin, T., Chen, F., Lei, P., & Zhang, Q. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04254-9 · Cited by 64 · see citing works
“In addition, the interaction of Aβ and P-tau with dynamin-related protein 1 (Drp1) is the key factors in mitochondrial fragmentation, damage of mitochondria and synapsis, eventually possibly resulting in neuronal damage and cognitive deficit [71, 72].”
BackgroundProtective role of mitoquinone against impaired mitochondrial homeostasis in metabolic syndrome
Yang, J., Suo, H., & Song, J. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1809344 · Cited by 66 · see citing works
Fišar, Z., Hansíková, H., Křížová, J., Jirák, R., Kitzlerová, E., Zvěřová, M., Hroudová, J., Wenchich, L., Zeman, J., & Raboch, J. (2019) · Mitochondrion · doi:10.1016/j.mito.2019.07.013 · Cited by 63 · see citing works
Yang, J., Zhi, W., & Wang, L. (2024) · Molecules · doi:10.3390/molecules29122812 · Cited by 63 · see citing works
Advances in gene therapy approaches targeting neuro-inflammation in neurodegenerative diseases
Singh, K., Sethi, P., Datta, S., Chaudhary, J. S., kumar, S., V, Jain, D., Gupta, J. K., Kumar, S., Guru, A., & Panda, S. P. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102321 · Cited by 62 · see citing works
Guha, S., Fischer, S., Johnson, G., & Nehrke, K. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00410-7 · Cited by 50 · see citing works
“This observation is consistent with defective mitophagy being a prominent feature in age-related disorders [90], including AD [91, 92], and contributing to premature aging such as observed in Werner’s syndrome patients and invertebrate Werner’s disease models [93].”
BackgroundMitochondria in Alzheimer’s Disease Pathogenesis
Reiss, A. B., Gulkarov, S., Jacob, B., Srivastava, A., Pinkhasov, A., Gomolin, I. H., Stecker, M. M., Wısnıewskı, T., & Leon, J. D. (2024) · Life · doi:10.3390/life14020196 · Cited by 62 · see citing works
“A β and tau also interfere with the trafficking of mitochondria to and from the synapse while also fostering mitochondrial fission, leading to synaptic dysfunction [73,74].”
BackgroundMagnetic Resonance Texture Analysis in Alzheimer's disease
Cai, J., He, Y., Zhong, X., Lei, H., Wang, F., Luo, G.-H., Zhao, H., & Liu, J.-C. (2020) · Academic Radiology · doi:10.1016/j.acra.2020.01.006 · Cited by 62 · see citing works
Hossain, M. F., Wang, N., Chen, R., Li, S., Roy, J., Uddin, M. G., Li, Z., Lim, L. W., & Song, Y. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101304 · Cited by 62 · see citing works
Chiarini, A., Gui, L., Viviani, C., Armato, U., & Prà, I. D. (2023) · Biomedicines · doi:10.3390/biomedicines11040999 · Cited by 61 · see citing works
Lacombe, A., & Scorrano, L. (2024) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2024.02.001 · Cited by 64 · see citing works
Interaction between autophagy and the NLRP3 inflammasome in Alzheimer’s and Parkinson’s disease
Lu, R., Zhang, L., & Yang, X. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1018848 · Cited by 58 · see citing works
“Studies have found that Aβ deposition may lead to impaired trafficking and maturation of autophagic vacuoles, thereby hindering the neuroprotective function of autophagy (Reddy and Oliver, 2019).”
BackgroundCEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer’s disease
Xie, W., Guo, D. S., Li, J., Yue, L., Kang, Q., Chen, G., Zhou, T., Wang, H., Zhuang, K., Leng, L., et al. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-01027-7 · Cited by 57 · see citing works
Holder, K., & Reddy, P. H. (2020) · The Neuroscientist · doi:10.1177/1073858420960443 · Cited by 55 · see citing works
“…damage and apoptosis as a result of mitochondrial dysfunction (Saleh and others 2020; Singh and others 2020) In healthy subjects, mitochondrial turnover through mitophagy, an auto-phagocytic process, is critical for maintaining proper cellular functions (Ding and Yin 2012; Reddy and Oliver 2019).”
BackgroundSelf-citationCoelho, P., Fão, L., Mota, S. I., & Rego, A. C. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101667 · Cited by 57 · see citing works
Panda, C., Voelz, C., Habib, P., Mevissen, C., Pufe, T., Beyer, C., Gupta, S. K., & Slowik, A. (2021) · Cells · doi:10.3390/cells10071652 · Cited by 54 · see citing works
Aging-Dependent Mitophagy Dysfunction in Alzheimer’s Disease
Song, M., Zhao, X., & Song, F. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02248-y · Cited by 56 · see citing works
Kandimalla, R. J. L., Mańczak, M., Pradeepkiran, J. A., Morton, H., & Reddy, P. H. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab360 · Cited by 53 · see citing works
Self-citationRetractedTan, S., Wang, D., Fu, Y., Zheng, H., Liu, Y., & Lu, B. (2023) · 中国科学通报：英文版 · doi:10.1016/j.scib.2023.10.021 · Cited by 55 · see citing works
The role of microRNAs in diseases and related signaling pathways
Vaghf, A., Khansarinejad, B., Ghaznavi‐Rad, E., & Mondanizadeh, M. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06725-y · Cited by 51 · see citing works
DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders
Provasek, V. E., Mitra, J., Malojirao, V. H., & Hegde, M. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094653 · Cited by 51 · see citing works
Mitochondrial function and Aβ in Alzheimer's disease postmortem brain
Troutwine, B. R., Strope, T. A., Franczak, E., Lysaker, C. R., Hamid, L., Mansel, C., Stopperan, J. A., Gouvion, C. M., Haeri, M., Swerdlow, R. H., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105781 · Cited by 51 · see citing works
“We and others have reported strong relationships between APP processing, Aβ production, and mitochondrial function (Anandatheerthavarada et al., 2003; Bhattacharyya et al., 2021; Hansson Petersen et al., 2008; Rhein et al., 2009; Wilkins and Swerdlow, 2017).”
BackgroundMitochondria in Aging and Alzheimer’s Disease: Focus on Mitophagy
Pradeepkiran, J. A., Baig, J., Seman, A., & Reddy, P. H. (2023) · The Neuroscientist · doi:10.1177/10738584221139761 · Cited by 50 · see citing works
“The PINK1 64kDa protein detects mitochondrial quality (Deas and others 2011; Reddy and Oliver 2019).”
Self-citationYan, Y., Yan, H., Teng, Y., Wang, Q., Yang, P., Zhang, L., Cheng, H., & Fu, S. (2020) · The Journal of Gene Medicine · doi:10.1002/jgm.3268 · Cited by 49 · see citing works
“Micro RNAs (miRNAs), which are short single-stranded RNAs that regulate gene expression by binding lncRNAs or messenger RNAs (mRNAs) in various diseases,(15) are known to be associated with AD, including Tau phosphorylated modulation and Aβ accumulation, etc..(16) lncRNA NEAT1 exerts its functional role in regulating…”
BackgroundXu, Z., Elrashidy, R. A., Li, B., & Liu, G. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.812967 · Cited by 49 · see citing works
Xu, H., Zhou, Q., Liu, B., Cheng, K., Chen, F., & Wang, M. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c04049 · Cited by 50 · see citing works
Chen, N., Guo, Z., Luo, Z., Zheng, F., Shao, W., Yu, G., Cai, P., Wu, S., & Li, H. (2020) · Environmental Pollution · doi:10.1016/j.envpol.2020.116413 · Cited by 49 · see citing works
Mitochondrial protein dysfunction in pathogenesis of neurological diseases
Wang, L., Yang, Z., He, X., Pu, S., Yang, C., Wu, Q., Zhou, Z., Cen, X., & Zhao, H. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.974480 · Cited by 46 · see citing works
Liu, X., Ye, M., & Ma, L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1022821 · Cited by 48 · see citing works
Yang, J., Zhang, W., Zhang, S., Iyaswamy, A., Sun, J., Wang, J., & Yang, C. (2023) · Aging and Disease · doi:10.14336/ad.2022.0927 · Cited by 48 · see citing works
“Aging and Disease • Volume 14, Number 3, June 2023 656 phosphorylated Tau also compromises autophagy and mitophagy [32, 59] Tau can also be phosphorylated by increasing the mTOR activity.”
BackgroundUłamek-Kozioł, M., Czuczwar, S. J., Kocki, J., Januszewski, S., Bogucki, J., Bogucka‐Kocka, A., & Pluta, R. M. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190966 · Cited by 47 · see citing works
“Abnormalities in the expression of mitochondrial genes lead to mitochondria dysfunctions and are important in the progression and pathogenesis of AD [18].”
BackgroundResultInfluentialUbiquitin biology in neurodegenerative disorders: From impairment to therapeutic strategies
Kumar, D., Ambasta, R. K., & Kumar, P. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101078 · Cited by 49 · see citing works
Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders
Sukhorukov, V. S., Воронков, Д. Н., Baranich, T. I., Mudzhiri, N. M., Magnaeva, A., & Illarioshkin, S. N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910251 · Cited by 50 · see citing works
Xu, S., Yang, P., Qian, K., Li, Y., Guo, Q., Wang, P., Meng, R., Wu, J., Cao, J., Cheng, Y., et al. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.09.017 · Cited by 46 · see citing works
“Senile plaques composed of misfolded Aβ and neurofibrillary tangles formed by p-tau represent two main neuropathological hallmarks of AD, strongly indicating that the proteostasis defects play a critical role in the onset and progression of AD [2].”
BackgroundRole of mtDNA disturbances in the pathogenesis of Alzheimer’s and Parkinson’s disease
Antonyová, V., Kejík, Z., Brogyányi, T., Kaplánek, R., Pajková, M., Talianová, V., Hromádka, R., Masařík, M., Sýkora, D., Mikšátková, L., et al. (2020) · DNA Repair · doi:10.1016/j.dnarep.2020.102871 · Cited by 45 · see citing works
Kshirsagar, S., Alvir, R. V., Pradeepkiran, J. A., Hindle, A., Vijayan, M., Ramasubramaniam, B., Kumar, S., Reddy, A. P., & Reddy, P. H. (2022) · Cells · doi:10.3390/cells11172660 · Cited by 45 · see citing works
Self-citationRetractedThe complex relationship between gut microbiota and Alzheimer’s disease: A systematic review
Zhou, X.-P., Sun, L.-B., Liu, W., Zhu, W.-M., Li, L.-C., Song, X., Xing, J.-P., & Gao, S. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102637 · Cited by 50 · see citing works
“Furthermore, the disease process is also characterized by other pathological changes, such as neuroinflammation, deregulated microRNAs, mitochondrial damage, synaptic dysfunction, and neuronal loss (Reddy and Oliver, 2019).”
- Authors
- Reddy, P. H., & Oliver, D. M.
- Affiliations
- Texas Tech University (US)
- Corresponding author
- Reddy, P. Hemachandra
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2019-05-22
- Volume
- 8
- Issue
- 5
- Pages
- 488
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC6562604
- OpenAlex
- W2945779890
- Semantic Scholar
- ec6d41e896d47b5146fe18dfe3a1a446d0217c61
- Cited by
- 496
- References
- 127
- Citations by year
- 2026: 54 · 2025: 81 · 2024: 77 · 2023: 79 · 2022: 80 · 2021: 72 · 2020: 47 · 2019: 6
- FWCI
- 6.02
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AG042178, AG047812, NS105473)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- Alzheimer's disease, amyloid-beta, hyperphosphorylated tau, mitophagy, mitochondrial dysfunction, Drp1, PINK1/Parkin pathway, mitochondrial fission, mitochondrial fusion, mitochondrial biogenesis, lipid peroxidation, cytochrome c oxidase, calcium dyshomeostasis, neurodegeneration
- MeSH terms
- Aging, Alzheimer Disease, Animals, Autophagy, Cell Line, Humans, Mitochondria, Neurons, Phosphorylation, Amyloid beta-Peptides, tau Proteins, Mice, Mitochondrial Dynamics, Mitophagy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
