Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease
Open accessAbstract
Dysregulation of autophagy, a cellular catabolic mechanism essential for degradation of misfolded proteins, has been implicated in multiple neurodegenerative diseases. However, the mechanisms that lead to the autophagy dysfunction are still not clear. Based on the results of a genome-wide screen, we show that reactive oxygen species (ROS) serve as common mediators upstream of the activation of the type III PI3 kinase, which is critical for the initiation of autophagy. Furthermore, ROS play an essential function in the induction of the type III PI3 kinase and autophagy in response to amyloid beta peptide, the main pathogenic mediator of Alzheimer's disease (AD). However, lysosomal blockage also caused by Abeta is independent of ROS. In addition, we demonstrate that autophagy is transcriptionally down-regulated during normal aging in the human brain. Strikingly, in contrast to normal aging, we observe transcriptional up-regulation of autophagy in the brains of AD patients, suggesting that there might be a compensatory regulation of autophagy. Interestingly, we show that an AD drug and an AD drug candidate have inhibitory effects on autophagy, raising the possibility that decreasing input into the lysosomal system may help to reduce cellular stress in AD. Finally, we provide a list of candidate drug targets that can be used to safely modulate levels of autophagy without causing cell death.
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AI-based quantitative modeling and integrative network analysis have been applied to assess autophagy and UPS-related pathways in AD models.
“To investigate these proteostatic disruptions, AI-based methods such as quantitative modeling and integrative network analysis have been applied to assess autophagy and UPS-related pathways in AD models52,53.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [52]
The Results report protein–protein interaction network analysis of autophagy regulators and analysis of their expression in AD patient brain samples (page not provided). The paper also describes a quantitative autophagy assay, but these passages do not establish AI-based quantitative modeling or an assessment of UPS-related pathways. (LLM, conf=0.84)
Experimental — accuracy not yet measuredExpression of several autophagy proteins, particularly Beclin1, ATG5, and ATG7, declines with age and is exacerbated in Alzheimer's disease.
“The expression of several autophagy proteins, in particular Beclin1, ATG5, and ATG7, decline with age, and is exacerbated in AD (Lipinski et al., 2010; Lucin et al., 2013; Pickford et al., 2008; Rubinsztein et al., 2011).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Lipinski et al., 2010
Expression of Beclin1, ATG5, and ATG7 decreases with age.
“The expression of these three proteins decreases with age (Lipinski et al., 2010), which may lead to an insufficiency in LANDO, establishing a putative risk factor for pathology.”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Lipinski et al., 2010
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
CellProfiler: image analysis software for identifying and quantifying cell phenotypes
Carpenter, A. E., Jones, T. R., Lamprecht, M. R., Clarke, C., Kang, I. H., Friman, O., Guertin, D. A., Chang, J. H., Lindquist, R. A., Moffat, J., et al. (2006) · Genome biology · doi:10.1186/gb-2006-7-10-r100 · Cited by 5,077 · see citing works
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,671 · see citing works
Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry
Ho, Y., Gruhler, A., Heilbut, A. M., Bader, G. D., Moore, L., Adams, S., Millar, A., Taylor, P. P., Bennett, K. L., Boutilier, K., et al. (2002) · Nature · doi:10.1038/415180a · Cited by 3,573 · see citing works
A comprehensive two-hybrid analysis to explore the yeast protein interactome
Ito, T., Chiba, T., Ozawa, R., Yoshida, M., Hattori, M., & Sakaki, Y. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061034498 · Cited by 3,566 · see citing works
Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy
Pattingre, S., Tassa, A., Qu, X., Garuti, R., Liang, X. H., Mizushima, N., Packer, M., Schneider, M. D., & Levine, B. (2005) · Cell · doi:10.1016/j.cell.2005.07.002 · Cited by 3,536 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection.
Li, C., & Wong, W. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.31 · Cited by 3,133 · see citing works
Self-citationRavikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., et al. (2004) · Nature Genetics · doi:10.1038/ng1362 · Cited by 2,347 · see citing works
Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
Scherz‐Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L., & Elazar, Z. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601623 · Cited by 2,101 · see citing works
Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species
Kane, D. J., Sarafian, T. A., Anton, R., Hahn, H., Gralla, E. B., Valentine, J. S., Örd, T., & Bredesen, D. E. (1993) · Science · doi:10.1126/science.8235659 · Cited by 1,671 · see citing works
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study
Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A., & Cuervo, A. M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.113 · Cited by 1,588 · 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
Pickford, F., Masliah, E., Britschgi, M., Lucin, K. M., Narasimhan, R., Jaeger, P. A., Small, S., Spencer, B., Rockenstein, E., Levine, B., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33585 · Cited by 1,186 · see citing works
Amyloid β-Protein Fibrillogenesis
Walsh, D. M., Hartley, D. M., Kusumoto, Y., Fezoui, Y., Condron, M. M., Lomakin, A., Benedek, G. B., Selkoe, D. J., & Teplow, D. B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.36.25945 · Cited by 1,046 · see citing works
Reddy, P. H., & Beal, M. F. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.002 · Cited by 975 · see citing works
FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells
Hara, T., Takamura, A., Kishi, C., Iemura, S.-I., Natsume, T., Guan, J., & Mizushima, N. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200712064 · Cited by 971 · see citing works
Liang, W. S., Reiman, E. M., Valla, J., Dunckley, T., Beach, T. G., Grover, A., Niedzielko, T. L., Schneider, L. E., Mastroeni, D., Caselli, R., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709259105 · Cited by 585 · see citing works
Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1
Shibata, M., Lu, T., Furuya, T., Degterev, A., Mizushima, N., Yoshimori, T., MacDonald, M., Yankner, B., & Yuan, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600364200 · Cited by 458 · see citing works
Self-citationEvolution of the Aging Brain Transcriptome and Synaptic Regulation
Loerch, P. M., Lu, T., Dakin, K. A., Vann, J. M., Isaacs, A., Geula, C., Wang, J., Pan, Y., Gabuzda, D. H., Li, C., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003329 · Cited by 334 · see citing works
Self-citationLiang, W. S., Dunckley, T., Beach, T. G., Grover, A., Mastroeni, D., Ramsey, K., Caselli, R. J., Kukull, W. A., McKeel, D., Morris, J. C., et al. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.00242.2007 · Cited by 309 · see citing works
ABAD enhances Aβ‐induced cell stress via mitochondrial dysfunction
Takuma, K., Yao, J., Huang, J., Xu, H., Chen, X., Luddy, J. S., Trillat, A., Stern, D. M., Arancio, O., & Yan, S. S. (2005) · The FASEB Journal · doi:10.1096/fj.04-2582fje · Cited by 254 · see citing works
Autophagy promotes synapse development in <i>Drosophila</i>
Shen, W., & Ganetzky, B. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200907109 · Cited by 252 · see citing works
Lipinski, M. M., Hoffman, G., Ng, A., Zhou, W., Py, B. F., Hsu, E., Liu, X., Eisenberg, J. M., Liu, J. S., Blenis, J., et al. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.05.005 · Cited by 223 · see citing works
Self-citationControl of basal autophagy by calpain1 mediated cleavage of ATG5
Xia, H., Zhang, L., Chen, G., Zhang, T., Liu, J., Jin, M., Ma, X., Ma, D., & Yuan, J. (2010) · Autophagy · doi:10.4161/auto.6.1.10326 · Cited by 194 · see citing works
Self-citationAutophagy protects neuron from Aβ-induced cytotoxicity
Hung, S.-Y., Huang, W.-P., Liou, H., & Fu, W.-M. (2009) · Autophagy · doi:10.4161/auto.5.4.8096 · Cited by 135 · see citing works
Zhou, X., Babu, J. R., da Silva, S., Shu, Q., Graef, I. A., Oliver, T., Tomoda, T., Tani, T., Wooten, M. W., & Wang, F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701402104 · Cited by 122 · see citing works
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Hallmarks of aging: An expanding universe
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023) · Cell · doi:10.1016/j.cell.2022.11.001 · Cited by 6,549 · see citing works
Autophagy in Human Health and Disease
Choi, A. M. K., Ryter, S. W., & Levine, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1205406 · Cited by 2,583 · see citing works
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107 · see citing works
Autophagy in healthy aging and disease
Aman, Y., Schmauck-Medina, T., Hansen, M., Morimoto, R. I., Simon, A. K., Bjedov, I., Palikaras, K., Simonsen, A., Johansen, T., Tavernarakis, N., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00098-4 · Cited by 1,313 · see citing works
Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging
Green, D. R., Galluzzi, L., & Kroemer, G. (2011) · Science · doi:10.1126/science.1201940 · Cited by 1,245 · see citing works
Autophagy and apoptosis dysfunction in neurodegenerative disorders
Ghavami, S., Shojaei, S., Yeganeh, B., Ande, S. R., Jangamreddy, J. R., Mehrpour, M., Christoffersson, J., Chaabane, W., Moghadam, A. R., Kashani, H. H., et al. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.10.004 · Cited by 1,039 · see citing works
Mitophagy: mechanisms, pathophysiological roles, and analysis
Ding, W.-X., & Yin, X.-M. (2012) · bchm · doi:10.1515/hsz-2012-0119 · Cited by 1,032 · see citing works
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Yuan, J., Amin, P., & Ofengeim, D. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0093-1 · Cited by 967 · see citing works
Self-citationAutophagy as a promoter of longevity: insights from model organisms
Hansen, M., Rubinsztein, D. C., & Walker, D. W. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0033-y · Cited by 754 · see citing works
Overexpression of Atg5 in mice activates autophagy and extends lifespan
Pyo, J.-O., Yoo, S.-M., Ahn, H.-H., Nah, J., Hong, S.-H., Kam, T.-I., Jung, S., & Jung, Y.-K. (2013) · Nature Communications · doi:10.1038/ncomms3300 · Cited by 721 · see citing works
Lee, J.-H., Yang, D.-S., Goulbourne, C. N., Im, E., Stavrides, P., Pensalfini, A., Chan, H., Bouchet-Marquis, C., Bleiwas, C., Berg, M. J., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01084-8 · Cited by 638 · see citing works
Heckmann, B. L., Teubner, B. J. W., Tummers, B., Boada-Romero, E., Harris, L., Yang, M., Guy, C. S., Zakharenko, S. S., & Green, D. R. (2019) · Cell · doi:10.1016/j.cell.2019.05.056 · Cited by 503 · see citing works
“The expression of these three proteins decreases with age (Lipinski et al., 2010), which may lead to an insufficiency in LANDO, establishing a putative risk factor for pathology.”
Autophagy and the cell biology of age-related disease
Leidal, A. M., Levine, B., & Debnath, J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0235-8 · Cited by 424 · see citing works
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Garatachea, N., Pareja-Galeano, H., Sanchis-Gomar, F., Santos-Lozano, A., Fiuza-Luces, C., Morán, M., Emanuele, E., Joyner, M. J., & Lucia, A. (2015) · Rejuvenation Research · doi:10.1089/rej.2014.1623 · Cited by 413 · see citing works
Bordi, M., Berg, M. J., Mohan, P. S., Peterhoff, C. M., Alldred, M. J., Che, S., Ginsberg, S. D., & Nixon, R. A. (2016) · Autophagy · doi:10.1080/15548627.2016.1239003 · Cited by 353 · see citing works
Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging
Plaza-Zabala, A., Sierra-Torre, V., & Sierra, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030598 · Cited by 323 · see citing works
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Sikora, E., Bielak-Zmijewska, A., Dudkowska, M., Krzystyniak, A., Mosieniak, G., Wesierska, M., & Wlodarczyk, J. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.646924 · Cited by 304 · see citing works
Han, X., Tai, H., Wang, X., Wang, Z., Zhou, J., Wei, X., Ding, Y., Gong, H., Mo, C., Zhang, J., et al. (2016) · Aging Cell · doi:10.1111/acel.12446 · Cited by 302 · see citing works
Lenoir, O., Jasiek, M., Hénique, C., Guyonnet, L., Hartleben, B., Bork, T., Chipont, A., Flosseau, K., Bensaada, I., Schmitt, A., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1049799 · Cited by 296 · see citing works
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Piras, A., Collin, L., Grüninger, F., Graff, C., & Rönnbäck, A. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0292-9 · Cited by 271 · see citing works
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Kaarniranta, K., Salminen, A., Haapasalo, A., Soininen, H., & Hiltunen, M. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101908 · Cited by 248 · see citing works
Shin, J. Y., Park, H. J., Kim, H. N., Oh, S. H., Bae, J.-S., Ha, H.-J., & Lee, P. H. (2014) · Autophagy · doi:10.4161/auto.26508 · Cited by 243 · see citing works
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Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death
Liu, S., Sarkar, C., Dinizo, M., Faden, A. I., Koh, E. Y., Lipinski, M. M., & Wu, J. (2015) · Cell Death & Disease · doi:10.1038/cddis.2014.527 · Cited by 209 · see citing works
Self-citationAutophagy in Alzheimer’s disease
Zare-shahabadi, A., Masliah, E., Johnson, G. V. W., & Rezaei, N. (2015) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0076 · Cited by 204 · see citing works
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Salvadores, N., Sanhueza, M., Manque, P., & Court, F. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00451 · Cited by 182 · see citing works
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2012.11.004 · Cited by 173 · see citing works
Carvalho, C., Santos, M. S., Oliveira, C. R., & Moreira, P. I. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.05.001 · Cited by 145 · see citing works
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Yamamoto, T., Takabatake, Y., Kimura, T., Takahashi, A., Namba, T., Matsuda, J., Minami, S., Kaimori, J.-Y., Matsui, I., Kitamura, H., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1159376 · Cited by 135 · see citing works
Caloric restriction: Beneficial effects on brain aging and Alzheimer’s disease
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Noncanonical function of an autophagy protein prevents spontaneous Alzheimer’s disease
Heckmann, B. L., Teubner, B. J. W., Boada-Romero, E., Tummers, B., Guy, C., Fitzgerald, P., Mayer, U., Carding, S., Zakharenko, S. S., Wileman, T., et al. (2020) · Science Advances · doi:10.1126/sciadv.abb9036 · Cited by 114 · see citing works
Di Domenico, F., Barone, E., Perluigi, M., & Butterfield, D. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6759 · Cited by 114 · see citing works
Lo, C. H., & Zeng, J. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00362-0 · Cited by 117 · see citing works
Are there roles for brain cell senescence in aging and neurodegenerative disorders?
Tan, F. C. C., Hutchison, E. R., Eitan, E., & Mattson, M. P. (2014) · Biogerontology · doi:10.1007/s10522-014-9532-1 · Cited by 116 · see citing works
Lachance, V., Wang, Q., Sweet, E., Choi, I., Cai, C.-Z., Zhuang, X.-X., Zhang, Y., Jiang, J. L., Blitzer, R. D., Bozdagi-Gunal, O., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0342-4 · Cited by 96 · see citing works
Neuroprotective effects of dietary restriction: Evidence and mechanisms
Pani, G. (2015) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.03.004 · Cited by 103 · see citing works
Rapamycin and Alzheimer disease: a double-edged sword?
Carosi, J. M., & Sargeant, T. J. (2019) · Autophagy · doi:10.1080/15548627.2019.1615823 · Cited by 99 · see citing works
Dysregulated autophagy contributes to caspase-dependent neuronal apoptosis
Chung, Y., Lee, J., Jung, S., Lee, Y., Cho, J. W., & Oh, Y. J. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-1229-y · Cited by 99 · see citing works
Qin, Y., Liu, Y., Hao, W., Decker, Y., Tomic, I., Menger, M. D., Liu, C., & Fassbender, K. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600873 · Cited by 90 · see citing works
Enhancing autophagy in Alzheimer's disease through drug repositioning
Eshraghi, M., Ahmadi, M., Afshar, S., Lorzadeh, S., Adlimoghaddam, A., Rezvani Jalal, N., West, R., Dastghaib, S., Igder, S., Torshizi, S. R. N., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108171 · Cited by 89 · see citing works
Ren, F., Wei, J., Chen, Q., Hu, M., Yu, L., Mi, J., Zhou, X., Qin, D., Wu, J., & Wu, A. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.07.030 · Cited by 97 · see citing works
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Walters, H. E., & Cox, L. S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082325 · Cited by 85 · see citing works
Mitochondrial function and mitochondrial DNA maintenance with advancing age
Gaziev, A. I., Abdullaev, S., & Podlutsky, A. (2014) · Biogerontology · doi:10.1007/s10522-014-9515-2 · Cited by 77 · see citing works
Qi, H., Shen, D., Jiang, C., Wang, H., & Chang, M. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135493 · Cited by 76 · see citing works
Transcriptomic profiles of aging in purified human immune cells
Reynolds, L. M., Ding, J., Taylor, J. R., Lohman, K., Soranzo, N., de la Fuente, A., Liu, T. F., Johnson, C., Barr, R. G., Register, T. C., et al. (2015) · BMC Genomics · doi:10.1186/s12864-015-1522-4 · Cited by 62 · see citing works
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Hamano, T., Hayashi, K., Shirafuji, N., & Nakamoto, Y. (2018) · Current Alzheimer Research · doi:10.2174/1567205015666181004143432 · Cited by 57 · see citing works
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Hu, M.-L., Pan, Y.-R., Yong, Y.-Y., Liu, Y., Yu, L., Qin, D.-L., Qiao, G., Law, B. Y.-K., Wu, J.-M., Zhou, X.-G., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102078 · Cited by 44 · see citing works
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Danna, R., Kondle, S., Amar, O., Mabourakh, M., Chen, G., Fadol, W. B., & Mohieldin, A. M. (2025) · Biology · doi:10.3390/biology14121787 · Cited by 2 · see citing works
“Key consequences include impaired autophagy and reduced resistance to oxidative stress, both of which contribute to mitochondrial dysfunction and heightened vulnerability to neurodegenerative diseases [291–293].”
- Authors
- Lipinski, M. M., Zheng, B., Lu, T., Yan, Z., Py, B. F., Ng, A., Xavier, R. J., Li, C., Yankner, B. A., Scherzer, C. R., & Yuan, J.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-07-26
- Volume
- 107
- Issue
- 32
- Pages
- 14164-14169
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2922576
- OpenAlex
- W2006840724
- Cited by
- 680
- References
- 28
- Citations by year
- 2026: 30 · 2025: 49 · 2024: 43 · 2023: 48 · 2022: 52 · 2021: 65 · 2020: 43 · 2019: 55 · 2018: 56 · 2017: 39 · 2016: 53 · 2015: 37 · 2014: 30 · 2013: 31 · 2012: 25
- FWCI
- 18.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- HAL (submittedVersion)
- Funders
- National Institute on Aging (R37AG012859, P01AG027916)
- National Institute of Allergy and Infectious Diseases (AI 062773, R01AI062773)
- National Institute of Diabetes and Digestive and Kidney Diseases ((DK043351, P30DK043351, P30DK040561)
- National Institute of Neurological Disorders and Stroke (R01NS064155, P01NS058793, R21NS060227)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- autophagy, Alzheimer's disease, brain aging, reactive oxygen species, amyloid-beta, therapeutic target, neurodegeneration
- MeSH terms
- Aging, Alzheimer Disease, Autophagy, Brain, Gene Expression Regulation, Humans, Lysosomes, Amyloid beta-Peptides, Reactive Oxygen Species, Phosphatidylinositol 3-Kinases, Genome-Wide Association Study
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 ›
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