ArticleNature communications2020
The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction.
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Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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64citing papers in PubMed
6.0field-weighted citation impact, top 3% of its field
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Who cites it
64 citing papers in PubMed, 83 citations in OpenAlex.
- Safety, Tolerability and Pharmacokinetics of Icapamespib, a Selective Epichaperome Inhibitor, in Healthy Adults.The journal of prevention of Alzheimer's disease · 2022Trial
- Salvianolic Acid a Disrupts the HSP90α-AKT-PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Prion-like Protein TDP-43: Mechanisms, Diagnosis, and Therapeutic Prospects.Pathogens (Basel, Switzerland) · 2026Review
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Targeting protein protein interactions and their modulators to enable new therapeutic strategies for human diseases.NPJ systems biology and applications · 2026Review
- Embracing diversity: Post-translational modifications, the chaperone code, and the emergence of new chaperone entities.Cell stress & chaperones · 2026Review
- Synaptic Chaperone Dysfunction as a Convergent Mechanism in Neurodegenerative and Psychiatric Disorders.Neuroscience insights · 2026Review
- Beyond Inhibition: Rebalancing the Hsp90 Chaperone Network as a Therapeutic Strategy for Alzheimer's Disease.Drug design, development and therapy · 2026Review
- Mapping Dysfunctional Protein-Protein Interactions in Disease.Journal of visualized experiments : JoVE · 2025Article
- PTMs as molecular encoders: reprogramming chaperones into epichaperomes for network control in disease.Trends in biochemical sciences · 2025Review
- In vivo imaging of heat shock protein 90: Diagnostic tool and support for Hsp90-targeted therapy.Cell stress & chaperones · 2025Review
- A Longitudinal Study of Sex Differences in a TDP-43 Mouse Model Reveals STI1 Regulation of TDP-43 Proteinopathy and Motor Deficits.Journal of neurochemistry · 2025Article
- Review
- Stress-inducible phosphoprotein 1 (Sti1/Stip1/Hop) sequesters misfolded proteins during stress.The FEBS journal · 2025Article
- Frontal cortex pyramidal neuron expression profiles differentiate the prodromal stage from progressive degeneration across the Alzheimer's disease spectrum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Alzheimer's Disease and Frontotemporal Dementia: A Review of Pathophysiology and Therapeutic Approaches.Journal of neuroscience research · 2025Review
- Unconventional receptor functions and location-biased signaling of the lactate GPCR in the nucleus.Life science alliance · 2025Article
- Radiosynthesis and Evaluation of [Journal of labelled compounds & radiopharmaceuticals · 2025Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
39 authors at 7 institutions in 1 country.
Maria Carmen Inda *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Suhasini Joshi *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Tai Wang *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-9984-9634
Alexander Bolaender *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Srinivasa GanduChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-8288-1523
John Koren IiiChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-6017-1763
Alicia Yue CheBrain and Mind Research Institute, Weill Cornell Medical College, New York, NY, 10065, USA.
Tony TaldoneChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Pengrong YanChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-0021-6461
Weilin SunChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Mohammad UddinChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Palak PanchalChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Matthew RioloChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Smit ShahChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Afsar BarlasMolecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Ke XuMolecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Lon Yin L ChanChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Alexandra GruzinovaChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Sarah KishinevskyChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Lorenz StuderDepartment of Developmental Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-0741-7987
Valentina FossatiThe New York Stem Cell Foundation Research Institute, New York, NY, 10019, USA.
Scott A NoggleThe New York Stem Cell Foundation Research Institute, New York, NY, 10019, USA.
Julie R WhiteComparative Pathology Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Elisa de StanchinaMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Sonia SequeiraOffice of Clinical Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-3473-0736
Kyle H AnthoneyDepartment of Biological Sciences, Humboldt State University, Arcata, CA, 95521, USA.
John W SteeleDepartment of Biological Sciences, Humboldt State University, Arcata, CA, 95521, USA.
Katia Manova-TodorovaMolecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Sujata PatilDepartment of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Mark P DunphyDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-1886-1832
NagaVaraKishore PillarsettyDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-1750-7436
Ana C PereiraDepartment of Neuroscience, Rockefeller University, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-2524-7969
Hediye Erdjument-BromageDepartment of Cell Biology, NYU School of Medicine, New York, NY, 10016, USA.ORCID http://orcid.org/0000-0003-0224-3594
Thomas A NeubertDepartment of Cell Biology, NYU School of Medicine, New York, NY, 10016, USA.
Anna RodinaChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Stephen D GinsbergDepartments of Psychiatry, Neuroscience & Physiology & the NYU Neuroscience Institute, NYU School of Medicine, New York, NY, 10016, USA.
Natalia De Marco GarciaBrain and Mind Research Institute, Weill Cornell Medical College, New York, NY, 10065, USA.
Wenjie LuoBrain and Mind Research Institute, Weill Cornell Medical College, New York, NY, 10065, USA. wel2009@med.cornell.edu.ORCID http://orcid.org/0000-0003-3752-8266
Gabriela ChiosisChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. chiosisg@mskcc.org.ORCID http://orcid.org/0000-0003-0486-6920
Memorial Sloan Kettering Cancer Center · USCornell University · USCal Poly Humboldt · USNew York Stem Cell Foundation · USNew York University · USNathan Kline Institute for Psychiatric Research · USRockefeller University · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MUncovering 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
$40.0MTAU, AB, SYNUCLEIN AND NITRATIVE/OXIDATIVE DAMAGE IN MCIP01AG014449 · NIA · UNIVERSITY OF PITTSBURGH · PI MUFSON, ELLIOTT JAY · 1997 to 2024
$39.7MMSKCC Pilot Center for Precision Disease ModelingU54OD020355 · OD · SLOAN-KETTERING INST CAN RESEARCH · PI LOWE, SCOTT W., SOLIT, DAVID B. · 2015 to 2019
$9.9MProject 3: Structural Basis for grp94 Drug Development and Chaperone FunctionP01CA186866 · NCI · OHIO STATE UNIVERSITY · PI GEWIRTH, DANIEL T · 2015 to 2019
$6.7MChaperome networks in Alzheimer's diseaseR01AG067598 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI ARANCIO, OTTAVIO, CHIOSIS, GABRIELA · 2021 to 2025
$5.9MNeural Mechanism for the assembly of GABAergic in the cerebral cortexR01MH110553 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI Natalia Vanesa De Marco Garcia · 2016 to 2026
$4.2MCellular and Molecular Medial Temporal Lobe Pathology in Elderly PreMCI subjectsR01AG043375 · NIA · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · PI GINSBERG, STEPHEN D, MUFSON, ELLIOTT JAY · 2013 to 2017
$3.6MSmall molecule Hsp90 inhibitors in AD treatmentU01AG032969 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA · 2010 to 2014
$3.5MTau pathology in Down syndrome and Alzheimer'sRF1AG061566 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER, MARGITTAI, MARTIN · 2019 to 2019
$3.4MBiomarkers for predicting response to Hsp90 therapyR01CA172546 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, DUNPHY, MARK P. · 2013 to 2017
$2.9MA chemical chaperomics platform for ADR56AG061869 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA · 2018 to 2019
$1.8MNCI NIH HHS P01 CA186866NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA172546NCRR NIH HHS S10 RR027990NIA NIH HHS K01 AG032364NIA NIH HHS K76 AG054772NIA NIH HHS P01 AG014449NIA NIH HHS P01 AG017617NIA NIH HHS R01 AG043375NIA NIH HHS R01 AG067598NIA NIH HHS R21 AG028811NIA NIH HHS R56 AG061869NIA NIH HHS RF1 AG061566NIA NIH HHS U01 AG032969NIH HHS U54 OD020355NIMH NIH HHS R01 MH110553
Abstract
Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.
Indexed as
Alzheimer DiseaseAnimalsBrainBrain MappingCognitive DysfunctionExecutive FunctionFemaleHippocampusHumansMaleMemoryMiceNeural PathwaysNeuronal PlasticityProteomeProteome
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