ArticleCell2021
Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 1 of them a synthesis that pooled it.
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220citing papers in PubMed, 1 pooled it
33.0field-weighted citation impact, top 1% of its field
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Who cites it
220 citing papers in PubMed, 1 synthesis or guideline pooled it, 303 citations in OpenAlex.
- Shift of the insoluble content of the proteome in the aging mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2023Pooled it
- Decline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cells.Nature aging · 2026Article
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- Synthesis of RARα-PROTAC and its delivery viaMaterials today. Bio · 2026Article
- Proteostasis and ageing dissidence.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Peptide-mediated inhibition of aberrant chaperone-mediated autophagy in pericytes prevents glioblastoma progression through MAPT/tau secretion.Autophagy · 2026Article
- LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026Review
- A destination-driven framework for nanoparticle-enabled targeted protein degradation.Acta pharmaceutica Sinica. B · 2026Review
- Gaps in the Parkinson's disease therapeutic clinical pipeline: A focus on approaches targeting disease pathobiology.Journal of Parkinson's disease · 2026Review
- Small bites for big problems: stepwise aggregate degradation by autophagy.Biochemical Society transactions · 2026Review
- Chaperone-mediated autophagy is a tumor-suppressive mechanism in hepatocellular carcinoma.Cell reports · 2026Article
- Methamphetamine hijacks chaperone-mediated autophagy to degrade GPX4, driving ferroptosis-precipitated cognitive decline and addictive pathogenesis.Acta neuropathologica communications · 2026Article
- SEC14L2 couples chaperone-mediated autophagy to microtubule stability by targeting Stathmin 1.Nature communications · 2026Article
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- CLN7 suppression induces apoptosis via mTOR-regulated and chaperone-mediated autophagy in myeloid leukemia cells.Cell death & disease · 2026Article
- Chaperone-mediated autophagy is required for regulatory T cell function.Nature communications · 2026Article
- β-Asarone, Tenuifolin, and YuanZhi Decoction Restore Cognitive Function and Modulate GRIN2B-Associated Autophagy in Alzheimer's Disease.Neurochemical research · 2026Article
160 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 3 countries.
Mathieu BourdenxDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: mathieu.bourdenx@u-bordeaux.fr.
Adrián Martín-SeguraDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Aurora ScrivoDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Jose A Rodriguez-NavarroDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Susmita KaushikDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Inmaculada TassetDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Antonio DiazDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Nadia J StormDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Qisheng XinDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Yves R JusteDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Erica StevensonDepartment of Cellular Molecular Pharmacology, School of Medicine and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; David Gladstone Institutes, San Francisco, CA 94158, USA.
Enrique LuengoDepartment of Pharmacology, School of Medicine, Instituto Teófilo Hernando for Drug Discovery, Universidad Autonoma de Madrid, Madrid 28049, Spain.
Cristina C ClementDepartment of Radiation Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Se Joon ChoiDepartment of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY 10461, USA.
Nevan J KroganDepartment of Cellular Molecular Pharmacology, School of Medicine and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; David Gladstone Institutes, San Francisco, CA 94158, USA.
Eugene V MosharovDepartment of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY 10461, USA.
Laura SantambrogioDepartment of Radiation Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Fiona GrueningerRoche Pharma Research and Early Development (pRED), Neuro-Immunology, Roche Innovation Center Basel, CH-4070, Switzerland.
Ludovic CollinRoche Pharma Research and Early Development (pRED), Neuro-Immunology, Roche Innovation Center Basel, CH-4070, Switzerland.
Danielle L SwaneyDepartment of Cellular Molecular Pharmacology, School of Medicine and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; David Gladstone Institutes, San Francisco, CA 94158, USA.
David SulzerDepartment of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY 10461, USA; Departments of Neurology and Pharmacology, Columbia University Medical Center, New York, NY 10032, USA.
Evripidis GavathiotisInstitute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: evripidis.gavathiotis@einsteinmed.org.
Ana Maria CuervoDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Studies of the Department of Medicine of the Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: ana-maria.cuervo@einsteinmed.org.
Albert Einstein College of Medicine · USColumbia University Irving Medical Center · USCornell University · USRoche (Switzerland) · CHUniversity of California, San Francisco · USNew York State Psychiatric InstituteQB3 · USUniversidad Autónoma de Madrid · ES
Funding
WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2MUncovering Alzheimer's disease risk mechanisms through neuron-specific analysis of autophagy and endosomal-lysosomal functionP01AG017617 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI NIXON, RALPH A. · 2000 to 2021
$40.0MRole of Autophagy in T Cell Function and Immunosenescence (Project 3)P01AG031782 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2009 to 2024
$36.2MTRAINING PROGRAM IN CELLULAR &MOLEC. BIOLOGY &GENETICST32GM007491 · NIGMS · YESHIVA UNIVERSITY · PI QUERY, CHARLES C · 1985 to 2021
$17.0MProject 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2016 to 2020
$10.8MEinstein's Nathan Shock Center of Excellence in Basic Biology of AgingP30AG038072 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI HUFFMAN, DEREK MAJOR · 2010 to 2024
$10.8MThe Dopamine Synapse and Associative LearningR01DA007418 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI David Sulzer · 1999 to 2026
$9.4MDecreased Protein Degradation in AgingR37AG021904 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2013 to 2022
$4.4MAutoimmune Features of Neurodegenerative DisordersR01NS095435 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SETTE, ALESSANDRO, SULZER, DAVID · 2018 to 2022
$4.2MDECREASED PROTEIN DEGRADATION IN AGINGR01AG021904 · NIA · YESHIVA UNIVERSITY · PI CUERVO, ANA MARIA · 2003 to 2012
$3.7MUnderstanding Alzheimer's Disease in the Context of the Aging BrainRF1AG054108 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CUERVO, ANA MARIA · 2016 to 2016
$2.1MConsole and probe upgrade for 600 MHz NMRS10OD016305 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI COWBURN, DAVID · 2014 to 2014
$595kNCI NIH HHS P30 CA013330NIA NIH HHS P01 AG017617NIA NIH HHS P01 AG031782NIA NIH HHS P30 AG038072NIA NIH HHS R01 AG021904NIA NIH HHS R37 AG021904NIA NIH HHS RF1 AG054108NIDA NIH HHS R01 DA007418NIGMS NIH HHS T32 GM007491NIH HHS S10 OD016305NINDS NIH HHS R01 NS095435NINDS NIH HHS U54 NS100717
Abstract
Components of the proteostasis network malfunction in aging, and reduced protein quality control in neurons has been proposed to promote neurodegeneration. Here, we investigate the role of chaperone-mediated autophagy (CMA), a selective autophagy shown to degrade neurodegeneration-related proteins, in neuronal proteostasis. Using mouse models with systemic and neuronal-specific CMA blockage, we demonstrate that loss of neuronal CMA leads to altered neuronal function, selective changes in the neuronal metastable proteome, and proteotoxicity, all reminiscent of brain aging. Imposing CMA loss on a mouse model of Alzheimer's disease (AD) has synergistic negative effects on the proteome at risk of aggregation, thus increasing neuronal disease vulnerability and accelerating disease progression. Conversely, chemical enhancement of CMA ameliorates pathology in two different AD experimental mouse models. We conclude that functional CMA is essential for neuronal proteostasis through the maintenance of a subset of the proteome with a higher risk of misfolding than the general proteome.
Indexed as
ProteostasisAgingAlzheimer DiseaseAnimalsBrainCasein Kinase IChaperone-Mediated AutophagyDisease Models, AnimalFemaleMaleMiceNeuronsProteomeCasein Kinase IProteomeagingAlzheimer’s diseasechaperoneschemical activators of autophagylysosomesneurodegenerationprotein aggregationproteotoxicitysupersaturated proteometau
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