The DOI matches its Crossref record; 286 of the 288 references it cites were found in a registry or an index.
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Open accessAbstract
Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective.
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“and permanent or transient endogenous defects in autophagy have been associated with embryonic lethality, developmental defects, and multiple pathological disorders, including (but not limited to) neurodegeneration, cancer, and cardiovascular disorders [812–817].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [813]
In the citing paper
“Molecular and histopathologic analyses of patient tissues demonstrate mislocalized or accumulated autophagy machinery, pathogenic mutations underlying familial neurodegenerative diseases disable known autophagy-related factors, and genetically ablating autophagy effectors produce neurodegeneration in cell and animal model systems [74–81], supporting a role for autophagy dysfunction in the devel”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [80]
In the citing paper
“The autophagic process is essential in preserving the homeostatic requirements of post‐mitotic neurons, both at the central and at the peripheral nervous system levels (Menzies et al, 2017; Scrivo et al, 2018; Mallucci et al, 2020)”
From Autophagy in major human diseases (2021) · cites this paper as Menzies et al, 2017
In the citing paper
“By analogy, a comparable phenotype has been described in Atg16l1 hypomorphic mice (Lv et al, 2014; Wu et al, 2016; Menzies et al, 2017).”
From Autophagy in major human diseases (2021) · cites this paper as Menzies et al, 2017
In the citing paper
“Aβ is targeted for autophagy‐dependent degradation within the lysosome, explaining why activation of autophagy reduces the burden of Aβ plaques in rodents (Boland et al, 2008; Menzies et al, 2017; Meng et al, 2019).”
From Autophagy in major human diseases (2021) · cites this paper as Menzies et al, 2017
In the citing paper
“However, autophagy appears to be causally implicated in the PSEN1 (presenilin 1)‐mediated conversion of APP (amyloid beta precursor protein) into Aβ (Yu et al, 2005), as well as in the non‐canonical secretion of Aβ into the extracellular space (Nilsson et al, 2013; Menzies et al, 2017).”
From Autophagy in major human diseases (2021) · cites this paper as Menzies et al, 2017
In the citing paper
“While autophagy proteins have been shown to impact the clearance of protein aggregates in neurons, most likely by the canonical autophagic process of aggrephagy (Frake et al., 2015; Menzies et al., 2017; Qaisiya et al., 2017; Sarkar et al., 2007; Sarkar et al., 2009; Webb et al., 2003; Yamamoto and Simonsen, 2011), effects in microglia of the CNS are more likely due to LANDO.”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Menzies et al., 2017
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Autophagy within the mushroom body protects from synapse aging in a non-cell autonomous manner
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“Similarly, the administration of nutraceutical compounds, such as pterostilbene in collagen 6 null mice promotes a proper autophagic flux exerting favorable outcomes on muscle (Metti et al., 2020).”
BackgroundTranscriptional regulation of autophagy and its implications in human disease
Lei, Y., & Klionsky, D. J. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01162-9 · Cited by 71
“Neurodegenerative disorders Deficient autophagy is highly correlated with neurodegenerative diseases due to the impaired clearance of aggregate-prone proteins such as the amyloid β-protein (Aβ) and MAPT/tau in Alzheimer disease (AD), SNCA/α-synuclein in Parkinson disease (PD) and mutant HTT (mHTT) in Huntington diseas…”
BackgroundProgrammed 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 76
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“The autophagy receptor SQSTM1 contains 3 domains that are crucial for its function in autophagy: an N-terminal Phox and Bem1 (PB1) domain that mediates its homo- and heterooligomerization, an LC3-interacting region (LIR) motif that mediates its interaction with the autophagy protein LC3, and a C-terminal ubiquitin-ass…”
BackgroundToxicity mechanisms of selected engineered nanoparticles on human neural cells in vitro
Lojk, J., Repas, J., Veranič, P., Bregar, V. B., & Pavlin, M. (2020) · Toxicology · doi:10.1016/j.tox.2020.152364 · Cited by 71
The Role of Free Radicals in Autophagy Regulation: Implications for Ageing
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“On the one hand, Aβ may be degraded by autophagy, as autophagy induction has been shown to reduce its levels [201].”
BackgroundActivation of G protein‐coupled receptor 30 protects neurons by regulating autophagy in astrocytes
Wang, X., Yue, J., Hu, L., Tian, Z., Zhang, K., Yang, L., Zhang, H., Guo, Y., Feng, B., Liu, H., et al. (2019) · Glia · doi:10.1002/glia.23697 · Cited by 71
“Accordingly, the maintenance of autophagy could be a therapeutic strategy for astrogliosis-induced brain injury and neurodegenerative diseases (Menzies et al., 2017).”
BackgroundGenetics and molecular mechanisms of frontotemporal lobar degeneration: an update and future avenues
Ferrari, R., Manzoni, C., & Hardy, J. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.006 · Cited by 74
“Different alterations of the waste disposal process have been associated with various neurodegenerative disorders including PD, AD, prion disease and Huntington’s disease (HD) (Menzies et al., 2017).”
Autophagy Modulators in Cancer Therapy
Buzun, K., Gornowicz, A., Lesyk, R., Bielawski, K., & Bielawska, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115804 · Cited by 68
Kovács, Z., Brunner, B., & Ari, C. (2021) · Nutrients · doi:10.3390/nu13072197 · Cited by 68
“For example, in mammals, this effect may be mediated through βHB-evoked inhibition of mTOR activity, activation of FOXOs (via both activation of SIRT1 and direct inhibition of Akt), and ketone body metabolism-evoked decrease in blood glucose and insulin levels, which also decrease the activity of IIS pathways [52,77,1…”
BackgroundInfluentialXu, L., Zhang, C., Jiang, N., He, D., Bai, Y., & Xin, Y. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27792 · Cited by 65
“It is the main mechanism to maintain cell homeostasis and participate in the occurrence of a variety of neurodegenerative diseases.(4) Inflammation is a basic response to tissue damage and infection, coordinating the host defense and repair process through different inflammatory factors.”
BackgroundZhu, Y., Shan, X., Safarpour, F., Go, N. E., Li, N., Shan, A., Huang, M. C., Deen, M. C., Holicek, V., Ashmus, R. A., et al. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00015 · Cited by 66
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“Autophagy is an energydemanding pathway that is important for neuronal homeostasis and housekeeping, as it removes damaged/misfolded proteins from the cytoplasm, delivering them to lysosomes (Menzies et al., 2017).”
BackgroundMallucci, G. R., Klenerman, D., & Rubinsztein, D. C. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-040320-120625 · Cited by 62
Self-citationAberrant regulation of autophagy in mammalian diseases
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Autophagy Dysregulation and Obesity-Associated Pathologies.
Namkoong, S., Cho, C., Semple, I. A., & Lee, J. H. (2018) · PubMed Central · doi:10.14348/molcells.2018.2213 · Cited by 66
“In pancreatic beta cells, defects in autophagosomallysosomal fusion and lysosomal acidification were both observed after lipotoxic insults (Las et al., 2011; Mir et al., 2015).”
BackgroundNaoi, M., Inaba-Hasegawa, K., Shamoto‐Nagai, M., & Maruyama, W. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1797-5 · Cited by 66
“Activation of autophagy shows neuroprotection by cleavage of aggregation-prone proteins and damaged mitochondria, whereas impaired autophagy is associated with AD, PD, ALS, and polyglutamine disorders (Levine and Kroemer 2008; Menzies et al. 2017).”
BackgroundAhsan, A. U., Sharma, V. L., Wani, A., & Chopra, M. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01969-4 · Cited by 65
“As mentioned before, pharmacological or genetic approaches to enhance autophagy result in clearance of amyloid-β in various models [49].”
BackgroundlncRNA HOTAIR upregulates autophagy to promote apoptosis and senescence of nucleus pulposus cells
Zhan, S., Wang, K., Xiang, Q., Song, Y., Li, S., Liang, H., Luo, R., Wang, B., Liao, Z., Zhang, Y., et al. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29129 · Cited by 62
“Multiple studies have demonstrated that autophagy is involved in degenerative diseases, including diabetes, osteoarthritis, and neurodegeneration (Demirtas et al., 2016; Loeser, 2011; Menzies et al., 2017).”
BackgroundKim, S., Kim, D. K., Jeong, S., & Lee, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23115894 · Cited by 71
“Perturbation of autophagy has been suggested to be associated with aging and age-related neurodegenerative diseases, and genetic studies of autophagy-related genes have demonstrated autophagy’s critical involvement in neurodegenerative diseases [59,60].”
BackgroundSTING signaling in the brain: Molecular threats, signaling activities, and therapeutic challenges
Yang, K., Tang, Z., Xing, C., & Yan, N. (2023) · Neuron · doi:10.1016/j.neuron.2023.10.014 · Cited by 63
Synaptic activity protects against AD and FTD-like pathology via autophagic-lysosomal degradation
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“…damage of DA neurons may arise from oxidative stress (Jiang et al., 2016), autophagy-lysosomal dysfunction (Button et al., 2015; Wu et al., 2015; Menzies et al., 2017), endoplasmic reticulum (ER) stress (Celardo et al., 2016; Mercado et al., 2016), mitochondrial dysfunction (Abou-Sleiman et…”
BackgroundRole of Microgliosis and NLRP3 Inflammasome in Parkinson’s Disease Pathogenesis and Therapy
de Araújo, F. M., Cuenca‐Bermejo, L., Fernández‐Villalba, E., Costa, S. L., da Silva, V. D. A., & Herrero, M. T. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-01027-6 · Cited by 63
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Zinc in Cognitive Impairment and Aging
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Dual Leucine Zipper Kinase Inhibitors for the Treatment of Neurodegeneration
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On the Role of Basal Autophagy in Adult Neural Stem Cells and Neurogenesis
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“First, Atg5 binds to Atg12 in a reaction catalyzed by Atg7 and Atg10; the resulting complex is conjugated to Atg16L1 and is recruited to the pre-autophagosomal membrane by Eva1a/TMEM166 (Hu et al., 2016; Menzies et al., 2017).”
BackgroundPresenilins and γ-Secretase in Membrane Proteostasis
Oikawa, N., & Walter, J. (2019) · Cells · doi:10.3390/cells8030209 · Cited by 65
TFEB is a central regulator of the aging process and age-related diseases
Abokyi, S., Ghartey‐Kwansah, G., & Tse, D. Y. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101985 · Cited by 61
“, lipofuscin, α-synuclein, tau, and huntingtin), provide energy and building blocks for the biosynthesis, and inhibits oxidative stress (Cortes and La Spada, 2019; Menzies et al., 2017).”
Presynaptic endocytic factors in autophagy and neurodegeneration
Tehran, D. A., Kuijpers, M., & Haucke, V. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.12.018 · Cited by 58
PARP1 and Poly(ADP-ribosyl)ation Signaling during Autophagy in Response to Nutrient Deprivation
Rodríguez-Vargas, J. M., Oliver, F. J., & Dantzer, F. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2641712 · Cited by 63
“In vivo animal models of neuropathies have demonstrated that basal levels of autophagy are required for the continued health and normal function of neurons [34, 35].”
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Potential neuroprotection by Dendrobium nobile Lindl alkaloid in Alzheimer's disease models
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“A growing number of applications for trehalose are based on its bioprotective properties well-considered in the food, cosmetic, and pharmaceutical industries [470, 471].”
BackgroundProteostasis disturbance in amyotrophic lateral sclerosis
Medinas, D. B., Valenzuela, V., & Hetz, C. A. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx274 · Cited by 67
Targeting Alzheimer's disease with gene and cell therapies
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Protein aggregation in cell biology: An aggregomics perspective of health and disease
Cox, D., Raeburn, C., Sui, X., & Hatters, D. M. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.05.003 · Cited by 60
Belgrad, J., Pace, R. D., & Fields, R. D. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1066-19.2019 · Cited by 63
“Well characterized in neurons (Lee, 2012; Wong and Holzbaur, 2015; Maday and Holzbaur, 2016; Menzies et al., 2017), autophagy in glial cells has been much less studied.”
BackgroundRecent progress in the role of autophagy in neurological diseases
Meng, T., Lin, S., Zhuang, H., Huang, H., He, Z., Hu, Y., Gong, Q., & Feng, D. (2019) · Cell Stress · doi:10.15698/cst2019.05.186 · Cited by 58
Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease
Benn, C., & Dawson, L. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00242 · Cited by 59
Autophagy regulation by acetylation—implications for neurodegenerative diseases
Son, S. M., Park, S. J., Fernandez-Estévez, M., & Rubinsztein, D. C. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00556-4 · Cited by 59
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Defective mitophagy and the etiopathogenesis of Alzheimer’s disease
Zeng, K., Yu, X., Mahaman, Y. A. R., Wang, J., Liu, R., Li, Y., & Wang, X. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00305-1 · Cited by 62
“Molecular mechanisms of mitophagy Autophagy (meaning macroautophagy here) is a process through which double-membrane vesicles, called autophagosomes, deliver organelles and proteins to the lysosome for degradation [13].”
BackgroundChun, Y. S., Kim, M., Lee, S., Kim, M. J., Hong, T.-J., Jeon, J. K., Ganbat, D., Kim, H. T., Kim, S. S., Kam, T., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01713-5 · Cited by 56
CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis
Samelson, A. J., Ariqat, N., McKetney, J., Rohanitazangi, G., Bravo, C., Bose, R., Travaglini, K. J., Lam, V. L., Goodness, D., Ta, T., et al. (2026) · Cell · doi:10.1016/j.cell.2025.12.038 · Cited by 65
The Implications of Autophagy in Alzheimer’s Disease
Hamano, T., Hayashi, K., Shirafuji, N., & Nakamoto, Y. (2018) · Current Alzheimer Research · doi:10.2174/1567205015666181004143432 · Cited by 57
Agephagy – Adapting Autophagy for Health During Aging
Stead, E. R., Castillo-Quan, J. I., Martinez-Miguel, V. E., Lujan, C., Ketteler, R., Kinghorn, K. J., & Bjedov, I. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00308 · Cited by 61
“This highlights the importance of autophagy in removing damaged proteins in non-dividing neuronal tissue, and the potential of therapeutic autophagy enhancement in neurodegenerative disease (Menzies et al., 2017; Scrivo et al., 2018).”
BackgroundIonizing Radiation-Induced Brain Cell Aging and the Potential Underlying Molecular Mechanisms
Wang, Q., Yin, G., Huang, J., Xi, S.-J., Qian, F., Lee, R.-X., Peng, X., & Tang, F. R. (2021) · Cells · doi:10.3390/cells10123570 · Cited by 60
Maiti, P., Peruzzaro, S., Kolli, N., Andrews, M., Gharaibeh, A., Rossignol, J., & Dunbar, G. L. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14396 · Cited by 56
“of AD, which increased neuronal survival against toxic amyloid proteins [33-35].”
BackgroundPeroxisomal Dysfunction in Neurological Diseases and Brain Aging
Uzor, N.-E., McCullough, L. D., & Tsvetkov, A. S. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00044 · Cited by 61
“For instance, there is evidence that a sex difference exists in response to cerebral ischemia, or ischemic stroke, but it is unknown how these sex-associated differences may affect peroxisomes specifically (Siegel and McCullough, 2013; Mirza et al., 2015; Ritzel et al., 2017).”
BackgroundOpportunities for Therapeutic Modulation of O-GlcNAc
Cheng, S. S., Mody, A. C., & Woo, C. M. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00417 · Cited by 64
Wang, Z., Liu, J.-Y., Yang, C., Malampati, S., Huang, Y., Li, M., Li, M., & Song, J.-X. (2017) · Phytotherapy Research · doi:10.1002/ptr.5834 · Cited by 55
“Because targeting ALP has recently proposed as a promising strategy for PD and other neurodegenerative diseases (Menzies et al., 2017), the protective effects of genetically or pharmacologically activated ALP have been tested in experimental models of PD in recent years.”
BackgroundSevere white matter astrocytopathy in CADASIL
Hase, Y., Chen, A., Bates, L. L., Craggs, L., Yamamoto, Y., Gemmell, E., Oakley, A. E., Korolchuk, V. I., & Kalaria, R. N. (2018) · Brain Pathology · doi:10.1111/bpa.12621 · Cited by 58
“However, simultaneous accumulation of LC3 and the autophagic substrate p62 strongly argues that the changes we observe are likely to be due to the autophagy blockade, which has been implicated in a range of neurological pathologies and could result in the loss of cell viability (22).”
BackgroundCore autophagy genes and human diseases
Zhao, Y. G., & Zhang, H. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.08.003 · Cited by 55
Suthar, J. K., Vaidya, A., & Ravindran, S. (2022) · Journal of Applied Toxicology · doi:10.1002/jat.4317 · Cited by 57
Functional analyses of major cancer-related signaling pathways in Alzheimer's disease etiology
Guo, J., Cheng, J., North, B. J., & Wei, W. (2017) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2017.07.001 · Cited by 55
Sharma, J., di Ronza, A., Lotfi, P., & Sardiello, M. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080317-061804 · Cited by 57
Insights into C9ORF72-Related ALS/FTD from Drosophila and iPSC Models
Yuva-Aydemir, Y., Almeida, S., & Gao, F. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.04.002 · Cited by 52
Tang, D., Xu, Y., Wang, W., Yang, Z., Liu, B., Stadler, M., Liu, L.-L., & Gao, J. (2019) · Journal of Natural Products · doi:10.1021/acs.jnatprod.9b00091 · Cited by 55
Puri, C., Manni, M. M., Vicinanza, M., Hilcenko, C., Zhu, Y., Runwal, G., Stamatakou, E., Menzies, F. M., Mamchaoui, K., Bitoun, M., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.03.018 · Cited by 55
Self-citationAutophagy in Multiple Sclerosis: Two Sides of the Same Coin
Misrielal, C., Mauthe, M., Reggiori, F., & Eggen, B. J. L. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.603710 · Cited by 56
Gómez‐Sintes, R., Xin, Q., Jiménez‐Loygorri, J. I., McCabe, M., Díaz, A., Garner, T. P., Cotto-Rios, X. M., Wu, Y., Dong, S., Reynolds, C. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31869-1 · Cited by 60
Understanding and exploiting the roles of O-GlcNAc in neurodegenerative diseases
Pratt, M. R., & Vocadlo, D. J. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105411 · Cited by 56
“Moreover, impaired autophagy has been noted in both synucleinopathy and tauopathy models and patients (160).”
BackgroundAdvances in the study of the glymphatic system and aging
Xiong, Y., Yu, Q., Zhi, H., Peng, H., Xie, M., Li, R., Li, K., Ma, Y., & Sun, P. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14803 · Cited by 55
Hou, Y. H., Wang, J., & Feng, J. (2019) · Drug Design Development and Therapy · doi:10.2147/dddt.s194182 · Cited by 54
“Moreover, induction in autophagy has a beneficial effect against neurodegeneration,(28) which is associated with clearance of abnormal and misfolded proteins.(29,30)”
BackgroundFowler, P. C., Garcia-Pardo, M. E., Simpson, J. C., & O’Sullivan, N. C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01051 · Cited by 53
“The efficient initiation and completion of autophagy is essential for neuronal health which is reflected by the fact that a growing number of neurodegenerative diseases are characterized by autophagic dysfunction (Menzies et al., 2017).”
BackgroundMendelian neurodegenerative disease genes involved in autophagy
Stamatakou, E., Wróbel, L., Hill, S. M., Puri, C., Son, S. M., Fujimaki, M., Zhu, Y., Siddiqi, F. H., Fernandez-Estévez, M., Manni, M. M., et al. (2020) · Cell Discovery · doi:10.1038/s41421-020-0158-y · Cited by 52
Self-citationGlia-specific autophagy dysfunction in ALS
Strohm, L., & Behrends, C. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.024 · Cited by 57
Untangling the Tauopathy for Alzheimer’s disease and parkinsonism
Chang, H.-Y., Sang, T., & Chiang, A. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0457-x · Cited by 56
Wong, M. M. K., Beekhuis-Hoekstra, S. D., Vowles, J., Watson, L. M., Fuller, G. N., Nemeth, A. H., Cowley, S. A., Ansorge, O., Talbot, K., & Becker, E. B. E. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0600-7 · Cited by 53
Relevance of Autophagy and Mitophagy Dynamics and Markers in Neurodegenerative Diseases
Giorgi, C., Bouhamida, E., Danese, A., Previati, M., Pinton, P., & Patergnani, S. (2021) · Biomedicines · doi:10.3390/biomedicines9020149 · Cited by 51
“In addition, in recent years, the autophagy process has also been found to be particularly associated with neurodegeneration [11].”
BackgroundPircs, K., Drouin‐Ouellet, J., Horváth, V., Gil, J., Rezeli, M., Garza, R., Grassi, D. A., Sharma, Y., St‐Amour, I., Harris, K. L., et al. (2021) · Brain · doi:10.1093/brain/awab473 · Cited by 54
Influence of Long-Term Fasting on Blood Redox Status in Humans
de Toledo, F. W., Grundler, F., Goutzourelas, N., Tekos, F., Vassi, E., Mesnage, R., & Kouretas, D. (2020) · Antioxidants · doi:10.3390/antiox9060496 · Cited by 55
“In addition to autophagy activation, fasting and calorie restriction inhibit nuclear transcription factor-kB (NF-kB), the main regulator of inflammation, exerting anti-inflammatory activity [48,49].”
BackgroundA Compendium of Information on the Lysosome
Bouhamdani, N., Comeau, D., & Turcotte, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.798262 · Cited by 55
“Neurons are susceptible to the accumulation of cellular waste that cannot be diluted through cell division; thus, lysosomal function and positioning is an imperative process for neuronal health (Menzies et al., 2017).”
BackgroundOverhoff, M., Tellkamp, F., Heß, S., Tutas, J., Tolve, M., Faerfers, M., Ickert, L., Mohammadi, M., Bruyckere, E. D., Kallergi, E., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2022110963 · Cited by 52
“Autophagy is currently linked to neuronal function by mechanisms, which include its role in the clearance of damaged and/or defective intracellular components (Menzies et al , 2017).”
Chiu, C., Lu, C.-S., Weng, Y.-H., Chen, Y., Huang, Y., Chen, R., Cheng, Y., Huang, Y.-C., Liu, Y.-C., Lai, S., et al. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1118-5 · Cited by 53
Panda, P. K., Fahrner, A., Vats, S., Seranova, E., Sharma, V., Chipara, M., Desai, P., Torresi, J., Rosenstock, T., Kumar, D., et al. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00038 · Cited by 50
How do protein aggregates escape quality control in neurodegeneration?
Koopman, M. B., Ferrari, L., & Rüdiger, S. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.01.006 · Cited by 54
Assessment of Autophagy in Neurons and Brain Tissue
Benito‐Cuesta, I., Díez, H., Ordóñez‐Gutiérrez, L., & Wandosell, F. G. (2017) · Cells · doi:10.3390/cells6030025 · Cited by 52
“Several factors associate AD with dysfunctions in autophagy, such as the accumulation of amyloid and tau aggregates that might saturate the clearance system, or mutations in PS1 and PICALM that could affect lysosome activity or different steps in autophagy, respectively [60,65,71].”
BackgroundMethodInfluentialAutophagy dysfunctions associated with cancer cells and their therapeutic implications
Udriştioiu, A., & Nica-Badea, D. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108892 · Cited by 53
Wang, X., Zhu, P., Xu, S., Liu, Y., Yang, J., Yu, S., Wei, H., Li, J., Zhang, Q., Hasegawa, T., et al. (2019) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2019.105561 · Cited by 50
Autophagy and LRRK2 in the Aging Brain
Albanese, F., Novello, S., & Morari, M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01352 · Cited by 53
“Both clinical studies and preclinical models described neuronal atrophy, reduced cargo amount, impaired autophagy and mitophagy in age-related diseases (Boland and Nixon, 2006; Menzies et al., 2017; Boland et al., 2018).”
BackgroundFassio, A., Falace, A., Esposito, A., Aprile, D., Guerrini, R., & Benfenati, F. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00039 · Cited by 50
Pedrioli, G., & Paganetti, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.595515 · Cited by 50
PROTAC technology for the treatment of Alzheimer’s disease: advances and perspectives
Inuzuka, H., Liu, J., Wei, W., & Rezaeian, A.-H. (2022) · Acta Materia Medica · doi:10.15212/amm-2021-0001 · Cited by 52
“This mechanism expedites the degradation of cytoplasmic substrates such as misfolding proteins (aggrephagy), high loaded peroxisomes (perophagy), abnormal mitochondria (mitophagy) and pathogenic organisms (xenophagy) [19].”
BackgroundWang, G., Dai, G., Song, J., Zhu, M., Liu, Y., Hou, X., Ke, Z., Zhou, Y., Qiu, H., Wang, F., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00301 · Cited by 48
Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice
Zhu, Y., Huang, J., Chen, R., Zhang, Y., He, X., Duan, W.-X., Zou, Y.-L., Sun, M.-M., Sun, H., Cheng, S.-M., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02995-4 · Cited by 52
“Moderate autophagy is considered as a protective mechanism during the development of neurological disorders, while insufficient or excessive autophagy can be harmful to neurons [17–19].”
BackgroundSelf-citationChu, F., Li, K., Li, X., Xu, L., Huang, J., & Yang, Z. R. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03167-z · Cited by 50
Neurodegeneration Upon Dysfunction of Endosomal/Lysosomal CLC Chloride Transporters
Bose, S., He, H., & Stauber, T. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.639231 · Cited by 49
“Trafficking and function of these compartments is detrimental for cellular physiology and dysfunction of the degradative pathway, lysosomal clearance by exocytosis or autophagic delivery to this pathway are associated with neurodegenerative disorders (Hara et al., 2006; Komatsu et al., 2006; LaPlante et al., 2006; Nix…”
BackgroundUsing trehalose to prevent and treat metabolic function
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Hegde, R. N., Chiki, A., Petricca, L., Martufi, P., Arbez, N., Mouchiroud, L., Auwerx, J. H., Landles, C., Bates, G. P., Singh‐Bains, M. K., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2020104671 · Cited by 50
“…have shown that phosphorylation or introduction of phosphomimicking mutations at S13 and/or S16 inhibit the aggregation of mutant HTTex1 or HTTex1 model peptides (Gu et al, 2009; Mishra et al, 2012; Deguire et al, 2018) and increases HTTex1 conformational flexibility in vitro (Daldin et al, 2017).”
BackgroundSelf-citationLiu, X., Ye, M., & Ma, L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1022821 · Cited by 51
“Unlike other cell types, the normal function of neurons, which exhibits little or no division, relies heavily on autophagy, through which the damaged organelles and misfolded proteins can be successfully removed (Menzies et al., 2017).”
Background
Metadata
- Authors
- Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., Licitra, F., Lopez Ramirez, A., Pavel, M., Puri, C., Renna, M., Ricketts, T., Schlotawa, L., Vicinanza, M., Won, H., Zhu, Y., Skidmore, J., & Rubinsztein, D. C.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Rubinsztein, David C.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 93
- Issue
- 5
- Pages
- 1015-1034
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2592067246
- Cited by
- 1,134
- References
- 288
- Citations by year
- 2026: 68 · 2025: 96 · 2024: 107 · 2023: 119 · 2022: 153 · 2021: 138 · 2020: 145 · 2019: 159 · 2018: 108 · 2017: 39
- FWCI
- 16.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- Tau Consortium
- Alzheimer’s Research UK
- Wellcome Trust (095317/Z/11/Z)
- Cambridge Institute for Medical Research (100140/Z/12/Z)
- NIHR Biomedical Research Unit in Dementia at Addenbrooke’s Hospital
- The Rosetrees Trust
- FEBS
- Addenbrooke’s Charitable Trust
- Sims Scholarship
- James Baird Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- autophagy, neurodegeneration, lysosomal degradation, protein aggregation, neurodegenerative diseases, therapeutic target, druggable targets, mouse knockout models
- MeSH terms
- Animals, Autophagy, Humans, Lysosomes, Motor Neurons, Proteins, Signal Transduction, Neurodegenerative Diseases
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