Lysosomal Proteolysis and Autophagy Require Presenilin 1 and Are Disrupted by Alzheimer-Related PS1 Mutations
Open accessAbstract
Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autophagosome clearance during macroautophagy are prevented as a result of a selective impairment of autolysosome acidification and cathepsin activation. These deficits are caused by failed PS1-dependent targeting of the v-ATPase V0a1 subunit to lysosomes. N-glycosylation of the V0a1 subunit, essential for its efficient ER-to-lysosome delivery, requires the selective binding of PS1 holoprotein to the unglycosylated subunit and the Sec61alpha/oligosaccharyltransferase complex. PS1 mutations causing early-onset AD produce a similar lysosomal/autophagy phenotype in fibroblasts from AD patients. PS1 is therefore essential for v-ATPase targeting to lysosomes, lysosome acidification, and proteolysis during autophagy. Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets.
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?
The findings support an emerging concept that acidification impairment may be a proximal biochemical event in AD, common to multiple genetic risk factors that cause or promote AD.
“The findings support an emerging concept that acidification impairment may be a proximal biochemical event in AD, common to multiple genetic risk factors that cause or promote AD (Lee et al., 2010;Xue et al., 2014;Vidoni et al., 2016).”
From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Lee et al., 2010
The Discussion (page not available in our copy) links impaired lysosomal acidification to PS1 mutations that cause familial AD and suggests lysosomal dysfunction may also contribute to sporadic AD. It does not establish that acidification impairment is common to multiple distinct genetic risk factors for AD; its genetic findings concern PS1. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn familial AD caused by presenilin 1 (PSEN1) mutations, failed lysosomal delivery of the V0a1 subunit markedly impairs lysosomal acidification, inducing acid hydrolase inhibition and lysosomal substrate buildup in patient primary fibroblasts.
“in familial AD caused by presenilin 1 (PSEN1) mutations, failed lysosomal delivery of the V0a1 subunit markedly impairs lysosomal acidification, inducing acid hydrolase inhibition and lysosomal substrate buildup in patient primary fibroblasts ( Lee et al., 2010 ( Avrahami et al., 2013).”
From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Lee et al., 2010
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe PS1 holoprotein may facilitate N-glycosylation of the V0a1 subunit of V-ATPase and its trafficking from the endoplasmic reticulum to lysosomes, thereby promoting assembly and maturation of V-ATPase.
“It has been reported that the PS1 holoprotein may facilitate N-glycosylation of the V0a1 subunit of V-ATPase and its trafficking from the endoplasmic reticulum (ER) to lysosomes, thereby promoting the assembly and maturation of V-ATPase.266”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [266]
PS1 is essential for v-ATPase targeting to lysosomes and lysosome acidification.
“The Nixon laboratory has demonstrated that PS1 is essential for v-ATPase targeting to lysosomes and lysosome acidification3637.”
From Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease (2017) · cites this paper as [36]
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
1 retracted
Ramachandran, N., Munteanu, I., Wang, P., Aubourg, P., Rilstone, J. J., Israelian, N., Naranian, T., Paroutis, P., Guo, R., Ren, Z.-P., et al. (2009) · Cell · doi:10.1016/j.cell.2009.01.054 · Cited by 60 · see citing works
RetractedAutophagy: process and functionPreprint
Mizushima, N. (2007) · Genes & Development · doi:10.1101/gad.1599207 · Cited by 3,964 · see citing works
Bjørkøy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Øvervatn, A., Stenmark, H., & Johansen, T. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507002 · Cited by 3,276 · see citing works
Ravikumar, 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
Kimura, S., Noda, T., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4451 · Cited by 2,278 · see citing works
Ohkuma, S., & Poole, B. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.7.3327 · Cited by 2,185 · see citing works
TOR, a central controller of cell growth.
Schmelzle, T., & Hall, M. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 2,044 · see citing works
Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T., & Sulzer, D. (2004) · Science · doi:10.1126/science.1101738 · Cited by 2,024 · cited 1× · see citing works
“…vacuoles (AVs), the general term for intermediate vesicular compartments in the process of autophagy, accumulate in several neurodegenerative diseases (Cuervo et al., 2004; Nixon et al., 2005; Ravikumar et al., 2004) but autophagy pathology in Alzheimer’s disease (AD) is exceptionally robust.”
Self-citationAutophagy: from phenomenology to molecular understanding in less than a decade
Klionsky, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2245 · Cited by 1,938 · see citing works
Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K., & Van Leuven, F. (1998) · Nature · doi:10.1038/34910 · Cited by 1,818 · see citing works
Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology
Forgac, M. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2272 · Cited by 1,626 · see citing works
The roles of intracellular protein-degradation pathways in neurodegeneration
Rubinsztein, D. C. (2006) · Nature · doi:10.1038/nature05291 · Cited by 1,625 · 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
Self-citationGrowing roles for the mTOR pathway
Sarbassov, D. D., Ali, S. M., & Sabatini, D. M. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.009 · Cited by 1,556 · see citing works
Seglen, P. O., & Gordon, P. B. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.6.1889 · Cited by 1,360 · see citing works
Yoshimori, T., Yamamoto, A., Moriyama, Y., Futai, M., & Tashiro, Y. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47429-2 · Cited by 1,334 · see citing works
Yamamoto, A., Tagawa, Y., Yoshimori, T., Moriyama, Y., Masaki, R., & Tashiro, Y. (1998) · Cell Structure and Function · doi:10.1247/csf.23.33 · Cited by 1,312 · see citing works
Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997) · Nature Medicine · doi:10.1038/nm0197-67 · Cited by 1,271 · see citing works
Self-citationThe vacuolar (H+)-ATPases — nature's most versatile proton pumps
Nishi, T., & Forgac, M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm729 · Cited by 1,197 · see citing works
Boland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H., & Nixon, R. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0800-08.2008 · Cited by 1,119 · see citing works
Self-citationRab7: A Key to Lysosome Biogenesis
Bucci, C., Thomsen, P., Nicoziani, P., McCarthy, J., & van Deurs, B. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.2.467 · Cited by 1,084 · see citing works
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease
Yu, W. H., Cuervo, A. M., Kumar, A., Peterhoff, C. M., Schmidt, S. D., Lee, J.-H., Mohan, P. S., Mercken, M., Farmery, M. R., Tjernberg, L. O., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200505082 · Cited by 967 · see citing works
Self-citationSaura, C. A., Choi, S.-Y., Beglopoulos, V., Malkani, S., Zhang, D., Rao, B. S. S., Chattarji, S., Kelleher, R. J., Kandel, E. R., Duff, K., et al. (2004) · Neuron · doi:10.1016/s0896-6273(04)00182-5 · Cited by 757 · see citing works
An evolving view of the eukaryotic oligosaccharyltransferase
Kelleher, D. J., & Gilmore, R. (2005) · Glycobiology · doi:10.1093/glycob/cwj066 · Cited by 528 · see citing works
Shen, J., & Kelleher, R. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608332104 · Cited by 485 · see citing works
The Itinerary of Autophagosomes: From Peripheral Formation to Kiss‐and‐Run Fusion with Lysosomes
Jahreiss, L., Menzies, F. M., & Rubinsztein, D. C. (2008) · Traffic · doi:10.1111/j.1600-0854.2008.00701.x · Cited by 453 · see citing works
Ruiz‐Cañada, C., Kelleher, D. J., & Gilmore, R. (2009) · Cell · doi:10.1016/j.cell.2008.11.047 · Cited by 391 · see citing works
Neurodegenerative lysosomal disorders: A continuum from development to late age
Nixon, R. A., Yang, D.-S., & Lee, J.-H. (2008) · Autophagy · doi:10.4161/auto.6259 · Cited by 362 · see citing works
Self-citationEffects of PS1 Deficiency on Membrane Protein Trafficking in Neurons
Naruse, S., Thinakaran, G., Luo, J.-J., Kusiak, J. W., Tomita, T., Iwatsubo, T., Qian, X., Ginty, D. D., Price, D. L., Borchelt, D. R., et al. (1998) · Neuron · doi:10.1016/s0896-6273(00)80637-6 · Cited by 355 · see citing works
Koike, M., Shibata, M., Waguri, S., Yoshimura, K., Tanida, I., Kominami, E., Gotow, T., Peters, C., von Figura, K., Mizushima, N., et al. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)61253-9 · Cited by 330 · see citing works
Self-citationVisualization of acidic organelles in intact cells by electron microscopy.
Anderson, R. G. W., Falck, J. R., Goldstein, J. L., & Brown, M. S. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.15.4838 · Cited by 250 · see citing works
Diwu, Z. J., Chen, C.-S., Zhang, C., Klaubert, D. H., & Haugland, R. P. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)80059-3 · Cited by 212 · see citing works
Herreman, A., Gassen, G. V., Bentahir, M., Nyabi, O., Craessaerts, K., Mueller, U., Annaert, W. G., & Strooper, B. D. (2003) · Journal of Cell Science · doi:10.1242/jcs.00292 · Cited by 195 · see citing works
Nakanishi, H., Tominaga, K., Amano, T., Hirotsu, I., Inoue, T., & Yamamoto, K. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1048 · Cited by 174 · see citing works
Esselens, C. W., Oorschot, V. M. J., Baert, V., Raemaekers, T., Spittaels, K., Serneels, L., Zheng, H., Säftig, P., Strooper, B. D., Klumperman, J., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200406060 · Cited by 170 · see citing works
Cataldo, A. M., Peterhoff, C. M., Schmidt, S. D., Terio, N. B., Duff, K., Beard, M. E., Mathews, P. M., & Nixon, R. A. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.8.821 · Cited by 157 · see citing works
Self-citationSamari, H. R., & Seglen, P. O. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.37.23758 · Cited by 145 · see citing works
Subcellular Distribution and Turnover of Presenilins in Transfected Cells
Zhang, J., Kang, D. E., Xia, W., Okochi, M., Mori, H., Selkoe, D. J., & Koo, E. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.20.12436 · Cited by 142 · see citing works
Isolation of autophagic vacuoles from rat liver: morphological and biochemical characterization
Marzella, L., Ahlberg, J., & Glaumann, H. (1982) · Journal of Cell Biology · doi:10.1083/jcb.93.1.144 · Cited by 141 · see citing works
Chen, C.-S., Chen, W. U., Zhou, M., et al. (2000) · Journal of Biochemical and Biophysical Methods · doi:10.1016/s0165-022x(00)00048-8 · Cited by 119 · see citing works
Wilson, C., Murphy, D. D., Giasson, B. I., Zhang, B., Trojanowski, J. Q., & Lee, V. M. ‐. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200403061 · Cited by 106 · see citing works
Presenilins and Alzheimer's disease
Kim, T.-W., & Tanzi, R. E. (1997) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(97)80089-x · Cited by 97 · see citing works
Regulation of intracellular protein degradation in IMR‐90 human diploid fibroblasts
Auteri, J. S., Okada, A., Bochaki, V., & Dice, J. (1983) · Journal of Cellular Physiology · doi:10.1002/jcp.1041150210 · Cited by 90 · see citing works
Kokkonen, N., Rivinoja, A., Kauppila, A., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406698200 · Cited by 82 · see citing works
Shioi, J., Georgakopoulos, A., Mehta, P. D., Kouchi, Z., Litterst, C. M., Baki, L., & Robakis, N. K. R. K. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04391.x · Cited by 78 · see citing works
Bolt, G. R., Kristensen, C., & Steenstrup, T. D. (2004) · Glycobiology · doi:10.1093/glycob/cwi032 · Cited by 56 · see citing works
Normal brain development in PS1 hypomorphic mice with markedly reduced γ-secretase cleavage of βAPP
Rozmahel, R. F., Huang, J., Chen, F., Liang, Y., Nguyen, V., Ikeda, M., Lévesque, G., Yu, G., Nishimura, M., Mathews, P. M., et al. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00267-6 · Cited by 49 · see citing works
Self-citationLaudon, H., Mathews, P. M., Karlström, H., Bergman, A., Farmery, M. R., Nixon, R. A., Winblad, B. G., Gandy, S., Lendahl, U., Lundkvist, J., et al. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02298.x · Cited by 48 · see citing works
Self-citationDifferential segregation of human and hamster cathepsin D in transfected baby-hàmster kidney cells
Isidoro, C., Horst, M., Baccino, F. M., et al. (1991) · Biochemical Journal · doi:10.1042/bj2730363 · Cited by 28 · see citing works
The vacuolar H+‐translocating ATPase of renal tubules contains a 115‐kDa glycosylated subunit
Gillespie, J. G., Ozanne, S. E., Percy, J. M., et al. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)80446-a · Cited by 21 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Kang DE Yoon IS Repetto E Busse T Yermian N Ie L Koo EH Presenilins Mediate Phosphatidylinositol 3-Kinase/AKT and ERK Activation via Select Signaling Receptors: selectivity of PS2 in platelet-derived growth factor signaling J Biol Chem 2005 280 31537 31547 16014629
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · see citing works
Self-citationBiological Functions of Autophagy Genes: A Disease Perspective
Levine, B., & Kroemer, G. (2019) · Cell · doi:10.1016/j.cell.2018.09.048 · Cited by 2,832 · see citing works
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationAutophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585 · see citing works
Self-citationLysosomes as dynamic regulators of cell and organismal homeostasis
Ballabio, A., & Bonifacino, J. S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0185-4 · Cited by 1,469 · see citing works
The Biology of Proteostasis in Aging and Disease
Labbadia, J., & Morimoto, R. I. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-033955 · Cited by 1,472 · 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 Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134 · see citing works
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138 · see citing works
“266 However, there are inconsistent views on a series of events caused by defects in PS1, including impaired maturation of V0a1 in lysosomes, V-ATPase dysfunction, and lysosomal acidi fi cation defects.”
BackgroundDegradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies
Ciechanover, A., & Kwon, Y. T. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.117 · Cited by 898 · see citing works
Mitophagy 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 · see citing works
Compromised autophagy and neurodegenerative diseases
Menzies, F. M., Fleming, A., & Rubinsztein, D. C. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3961 · Cited by 851 · see citing works
Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles
Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.22 · Cited by 842 · see citing works
The lysosome: from waste bag to potential therapeutic target
Appelqvist, H., Wäster, P., Kågedal, K., & Öllinger, K. (2013) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjt022 · Cited by 772 · see citing works
Alzheimer’s disease: A matter of blood–brain barrier dysfunction?
Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20171406 · Cited by 672 · 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
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
Self-citationColacurcio, D. J., & Nixon, R. A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.004 · Cited by 548 · see citing works
Self-citationAPF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p
Wang, K., Liu, C.-Y., Zhou, L.-Y., Wang, J.-X., Wang, M., Zhao, B., Zhao, W.-K., Xu, S.-J., Fan, L.-H., Zhang, X.-J., et al. (2015) · Nature Communications · doi:10.1038/ncomms7779 · Cited by 473 · see citing works
Krabbe, G., Halle, A., Matyash, V., Rinnenthal, J. L., Eom, G. D., Bernhardt, U., Miller, K. R., Prokop, S., Kettenmann, H., & Heppner, F. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060921 · Cited by 478 · see citing works
Modeling Alzheimer’s disease with iPSC-derived brain cells
Penney, J., Ralvenius, W. T., & Tsai, L.-H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0468-3 · Cited by 471 · see citing works
Aβ Secretion and Plaque Formation Depend on Autophagy
Nilsson, P., Loganathan, K., Sekiguchi, M., Matsuba, Y., Hui, K., Tsubuki, S., Tanaka, M., Iwata, N., Saito, T., & Saido, T. C. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.08.042 · Cited by 459 · see citing works
Ageing, Cellular Senescence and Neurodegenerative Disease
Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102937 · Cited by 448 · see citing works
Synapses and Alzheimer's Disease
Sheng, M., Sabatini, B. L., & Sudhof, T. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005777 · Cited by 436 · see citing works
The Autophagy–Lysosomal Pathway in Neurodegeneration: A TFEB Perspective
Martini-Stoica, H., Xu, Y., Ballabio, A., & Zheng, H. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.02.002 · Cited by 436 · see citing works
Animal Models of Alzheimer Disease
LaFerla, F. M., & Green, K. N. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006320 · Cited by 419 · see citing works
Yang, D.-S., Stavrides, P., Mohan, P. S., Kaushik, S., Kumar, A., Ohno, M., Schmidt, S. D., Wesson, D., Bandyopadhyay, U., Jiang, Y., et al. (2011) · Brain · doi:10.1093/brain/awq341 · Cited by 429 · see citing works
Self-citationAutophagy 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
Nixon, R. A. (2017) · The FASEB Journal · doi:10.1096/fj.201700359 · Cited by 400 · see citing works
Self-citationMechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases
Nixon, R. A., & Rubinsztein, D. C. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00757-5 · Cited by 435 · see citing works
Self-citationAutophagy in lysosomal storage disorders
Lieberman, A. P., Puertollano, R., Raben, N., Slaugenhaupt, S., Walkley, S. U., & Ballabio, A. (2012) · Autophagy · doi:10.4161/auto.19469 · Cited by 399 · see citing works
Lucin, K. M., O’Brien, C. E., Bieri, G., Czirr, E., Mosher, K. I., Abbey, R. J., Mastroeni, D. F., Rogers, J., Spencer, B., Masliah, E., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.046 · Cited by 374 · see citing works
Lee, J.-H., McBrayer, M. K., Wolfe, D. M., Haslett, L. J., Kumar, A., Sato, Y., Lie, P. P. Y., Mohan, P., Coffey, E. E., Kompella, U., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.050 · Cited by 358 · see citing works
Self-citationTau-targeting therapies for Alzheimer disease: Current status and future directions
Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00883-2 · Cited by 371 · 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
Self-citationAutophagy and neurodegeneration
Frake, R. A., Ricketts, T., Menzies, F. M., & Rubinsztein, D. C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73944 · Cited by 332 · 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
TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading
Martini-Stoica, H., Cole, A. L., Swartzlander, D. B., Chen, F., Wan, Y.-W., Bajaj, L., Bader, D. A., Lee, V. M. Y., Trojanowski, J. Q., Liu, Z., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20172158 · Cited by 253 · see citing works
Deconstruction for Reconstruction: The Role of Proteolysis in Neural Plasticity and Disease
Bingol, B., & Sheng, M. (2011) · Neuron · doi:10.1016/j.neuron.2010.11.006 · Cited by 275 · see citing works
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
Autophagy Impairment Induces Premature Senescence in Primary Human Fibroblasts
Kang, H. T., Lee, K. B., Kim, S. Y., Choi, H. R., & Park, S. C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023367 · Cited by 254 · see citing works
Mitophagy in Alzheimer’s disease: Molecular defects and therapeutic approaches
Mary, A., Eysert, F., Checler, F., & Chami, M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01631-6 · Cited by 244 · see citing works
Age-related macular degeneration (AMD): Alzheimer's disease in the eye?
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
Liu, D., Pitta, M., Jiang, H., Lee, J.-H., Zhang, G., Chen, X., Kawamoto, E. M., & Mattson, M. P. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.020 · Cited by 238 · see citing works
Self-citationHenry, A. G., Aghamohammadzadeh, S., Samaroo, H., Chen, Y., Mou, K., Needle, E., & Hirst, W. D. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv314 · Cited by 235 · see citing works
Targeting lysosomes in human disease: from basic research to clinical applications
Cao, M., Luo, X., Wu, K., & He, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00778-y · Cited by 225 · see citing works
Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice
Caballero, B., Bourdenx, M., Luengo, E., Diaz, A., Sohn, P. D., Chen, X., Wang, C., Juste, Y. R., Wegmann, S., Patel, B., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22501-9 · Cited by 223 · see citing works
Self-citationSanchez-Varo, R., Trujillo-Estrada, L., Sanchez-Mejias, E., Torres, M., Baglietto-Vargas, D., Moreno-Gonzalez, I., De Castro, V., Jimenez, S., Ruano, D., Vizuete, M., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0896-x · Cited by 222 · see citing works
Lysosomal cell death mechanisms in aging
Gómez-Sintes, R., Ledesma, M. D., & Boya, P. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.02.009 · Cited by 216 · see citing works
Coen, K., Flannagan, R. S., Baron, S., Carraro-Lacroix, L. R., Wang, D., Vermeire, W., Michiels, C., Munck, S., Baert, V., Sugita, S., et al. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201201076 · Cited by 208 · see citing works
Serrano‐Puebla, A., & Boya, P. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12966 · Cited by 204 · see citing works
The biosynthesis, signaling, and neurological functions of bile acids
Kiriyama, Y., & Nochi, H. (2019) · Biomolecules · doi:10.3390/biom9060232 · Cited by 204 · see citing works
Autophagy 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
Autophagy and Its Normal and Pathogenic States in the Brain
Yamamoto, A., & Yue, Z. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014149 · Cited by 204 · see citing works
Woodruff, G., Young, J. E., Martinez, F. J., Buen, F., Gore, A., Kinaga, J., Li, Z., Yuan, S. H., Zhang, K., & Goldstein, L. S. B. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.018 · Cited by 177 · see citing works
Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99)
Jiang, Y., Sato, Y., Im, E., Berg, M., Bordi, M., Darji, S., Kumar, A., Mohan, P. S., Bandyopadhyay, U., Diaz, A., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.0578-19.2019 · Cited by 166 · see citing works
Self-citationHung, C. O. Y., & Livesey, F. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.095 · Cited by 159 · see citing works
Endo‐lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease?
Whyte, L. S., Lau, A. A., Hemsley, K. M., Hopwood, J. J., & Sargeant, T. J. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.13935 · Cited by 150 · see citing works
Autophagy and misfolded proteins in neurodegeneration
Metcalf, D. J., García-Arencibia, M., Hochfeld, W. E., & Rubinsztein, D. C. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2010.11.003 · Cited by 138 · see citing works
Valapala, M., Wilson, C., Hose, S., Bhutto, I. A., Grebe, R., Dong, A., Greenbaum, S., Gu, L., Sengupta, S., Cano, M., et al. (2014) · Autophagy · doi:10.4161/auto.27292 · Cited by 144 · see citing works
Chandra, S., Jana, M., & Pahan, K. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.0054-18.2018 · Cited by 134 · see citing works
Autophagy Dysfunction in Alzheimer’s Disease: Mechanistic Insights and New Therapeutic Opportunities
Di Meco, A., Curtis, M. E., Lauretti, E., & Praticò, D. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.008 · Cited by 133 · see citing works
Lysosomal adaptation: how the lysosome responds to external cues
Settembre, C., & Ballabio, A. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016907 · Cited by 126 · see citing works
Xue, X., Wang, L.-R., Sato, Y., Jiang, Y., Berg, M., Yang, D.-S., Nixon, R. A., & Liang, X.-J. (2014) · Nano Letters · doi:10.1021/nl501839q · Cited by 125 · see citing works
Self-citationCholesterol impairs autophagy-mediated clearance of amyloid beta while promoting its secretion
Barbero-Camps, E., Roca-Agujetas, V., Bartolessis, I., de Dios, C., Fernández-Checa, J. C., Marí, M., Morales, A., Hartmann, T., & Colell, A. (2018) · Autophagy · doi:10.1080/15548627.2018.1438807 · Cited by 125 · see citing works
TRPV1 sustains microglial metabolic reprogramming in Alzheimer's disease
Lu, J., Zhou, W., Dou, F., Wang, C., & Yu, Z. (2021) · The EMBO Reports · doi:10.15252/embr.202052013 · Cited by 121 · see citing works
Zhang, X., Garbett, K., Veeraraghavalu, K., Wilburn, B., Gilmore, R., Mirnics, K., & Sisodia, S. S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0556-12.2012 · Cited by 122 · 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
Ambegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113 · see citing works
“Recent reports have demonstrated that disruption of the v-ATPase complex, through LOF of the V0 transmembrane domain, leads to increased number of lysosomes that are impaired in proteolysis (184) and causes progressive neurodegeneration (185) and enhanced sensitivity to Ab or tau (186).”
BackgroundNeuroprotective 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
Chung, S., Jeong, J.-H., Park, J.-C., Han, J. W., Lee, Y., Kim, J.-I., & Mook-Jung, I. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01295-y · Cited by 103 · see citing works
“Moreover, ADLP APP/PS1 and ADLP APT mice have a PSEN1 mutation that genetically disrupts autophagic fl ux 23 .”
Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis
Nassif, M., Valenzuela, V., Rojas-Rivera, D., Vidal, R., Matus, S., Castillo, K., Fuentealba, Y., Kroemer, G., Levine, B., & Hetz, C. (2014) · Autophagy · doi:10.4161/auto.28784 · Cited by 100 · see citing works
Glucocorticoid impairs mitochondrial quality control in neurons
Choi, G. E., & Han, H. J. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105301 · Cited by 95 · see citing works
Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease
Mariani, M. M., Malm, T., Lamb, R., Jay, T. R., Neilson, L., Casali, B., Medarametla, L., & Landreth, G. E. (2017) · Scientific Reports · doi:10.1038/srep42270 · Cited by 98 · see citing works
Wu, J. J., Cai, A., Greenslade, J. E., Higgins, N. R., Fan, C., Le, N. T. T., Tatman, M., Whiteley, A. M., Prado, M. A., Dieriks, B. V., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1917371117 · Cited by 86 · 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
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79 · see citing works
Im, E., Jiang, Y., Stavrides, P. H., Darji, S., Erdjument-Bromage, H., Neubert, T. A., Choi, J. Y., Wegiel, J., Lee, J.-H., & Nixon, R. A. (2023) · Science Advances · doi:10.1126/sciadv.adg1925 · Cited by 80 · see citing works
Self-citationTargeting autophagy in Alzheimer’s disease: Animal models and mechanisms
Zhang, X.-W., 澳门大学中华医药研究院中药质量研究国家重点实验室, 澳. 凼. 9., State Key Laboratory of Quality Research in Chinese Medicine, I. O. C. M. S., Zhu, X.-X., Tang, D.-S., Lu, J.-H., 佛山大学广东省动物分子设计与精准育种重点实验室, 广., & Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, G. E. T. C. O. G. P. (2023) · Zoological Research · doi:10.24272/j.issn.2095-8137.2023.294 · Cited by 77 · see citing works
“Mutations in the PS1 gene can lead to V-ATPase dysfunction and defective autolysosomal degradation in AD patient-derived cells (Lee et al., 2010).”
BackgroundCa2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer’s Disease
McDaid, J., Mustaly-Kalimi, S., & Stutzmann, G. E. (2020) · Cells · doi:10.3390/cells9122655 · Cited by 73 · see citing works
Chong, C.-M., Ke, M., Tan, Y., Huang, Z., Zhang, K., Ai, N., Ge, W., Qin, D., Lu, J.-H., & Su, H. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0945-7 · Cited by 66 · see citing works
Presenilin controls kinesin-1 and dynein function during APP-vesicle transport in vivo
Gunawardena, S., Yang, G., & Goldstein, L. S. B. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt237 · Cited by 66 · see citing works
Mallucci, 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 · see citing works
Jordà‐Siquier, T., Petrel, M., Kouskoff, V., Smailovic, U., Cordelières, F., Frykman, S., Müller, U., Mulle, C., & Barthet, G. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12546 · Cited by 63 · see citing works
Lysoplex: An efficient toolkit to detect DNA sequence variations in the autophagy-lysosomal pathway
Di Fruscio, G., Schulz, A., De Cegli, R., Savarese, M., Mutarelli, M., Parenti, G., Banfi, S., Braulke, T., Nigro, V., & Ballabio, A. (2015) · Autophagy · doi:10.1080/15548627.2015.1043077 · Cited by 62 · see citing works
Yang, Y., & Zhang, L. (2020) · Food & Function · doi:10.1039/c9fo02611h · Cited by 57 · see citing works
Recent 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 · see citing works
Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles
Deng, Z., Dong, Y., Zhou, X., Lu, J.-H., & Yue, Z. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.12.009 · Cited by 58 · see citing works
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 · see citing works
Mustaly-Kalimi, S., Gallegos, W., Marr, R. A., Gilman-Sachs, A., Peterson, D. A., Sekler, I., & Stutzmann, G. E. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2211999119 · Cited by 55 · see citing works
Tong, B. C.-K., Wu, A. J., Huang, A. S., Dong, R., Malampati, S., Iyaswamy, A., Krishnamoorthi, S., Sreenivasmurthy, S. G., Zhu, Z., Su, C., et al. (2022) · Autophagy · doi:10.1080/15548627.2021.1945220 · Cited by 49 · see citing works
Neurogenetics: Advancing the “Next-Generation” of Brain Research
Zoghbi, H. Y., & Warren, S. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.015 · Cited by 48 · see citing works
Winslow, A. R., Moussaud, S., Zhu, L., Post, K. L., Dickson, D. W., Berezovska, O., & McLean, P. J. (2014) · Brain · doi:10.1093/brain/awu119 · Cited by 48 · see citing works
Presenilins in synaptic function and disease.
Ho, A., & Shen, J. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.06.002 · Cited by 52 · see citing works
Sullivan, S. E., Liao, M., Smith, R. V., White, C., Lagomarsino, V. N., Xu, J., Taga, M., Bennett, D. A., De Jager, P. L., & Young-Pearse, T. L. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddy376 · Cited by 44 · see citing works
The pleiotropic roles of autophagy in Alzheimer’s disease: From pathophysiology to therapy
Festa, B. P., Barbosa, A. D., Rob, M., & Rubinsztein, D. C. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.07.011 · Cited by 41 · see citing works
Ma, D., Stokes, K., Mahngar, K., Domazet-Damjanov, D., Sikorska, M., & Pandey, S. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.07.004 · Cited by 39 · see citing works
- Authors
- Lee, J.-H., Yu, W. H., Kumar, A., Lee, S., Mohan, P. S., Peterhoff, C. M., Wolfe, D. M., Martinez-Vicente, M., Massey, A. C., Sovak, G., Uchiyama, Y., Westaway, D., Cuervo, A. M., & Nixon, R. A.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- Albert Einstein College of Medicine (US)
- Juntendo University (JP)
- University of Alberta (CA)
- Corresponding author
- Nixon, Ralph A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 141
- Issue
- 7
- Pages
- 1146-1158
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3647462
- OpenAlex
- W2112329697
- Cited by
- 1,212
- References
- 50
- Citations by year
- 2026: 63 · 2025: 73 · 2024: 51 · 2023: 70 · 2022: 78 · 2021: 98 · 2020: 83 · 2019: 90 · 2018: 78 · 2017: 74 · 2016: 68 · 2015: 68 · 2014: 67 · 2013: 75 · 2012: 87
- FWCI
- 58.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NYU Langone Medical Center
- National Institutes of Health
- National Institute on Aging (P01AG017617)
- 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 › Cell Biology › Cellular transport and secretion
- Keywords
- presenilin 1, Alzheimer's disease, macroautophagy, lysosomal proteolysis, autophagosome clearance, N-glycosylation, PS1 mutations, neuronal cell death, lysosomal storage
- MeSH terms
- Alzheimer Disease, Animals, Autophagy, Blastocyst, Cell Line, Glycosylation, Humans, Hydrolysis, Lysosomes, Neurons, Proteins, Vacuoles, Gene Deletion, Mice, Knockout, Vacuolar Proton-Translocating ATPases, Mice, Presenilin-1, Gene Knockout Techniques
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
