Nature Communications (Jan 2020)
The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction
- Maria Carmen Inda,
- Suhasini Joshi,
- Tai Wang,
- Alexander Bolaender,
- Srinivasa Gandu,
- John Koren III,
- Alicia Yue Che,
- Tony Taldone,
- Pengrong Yan,
- Weilin Sun,
- Mohammad Uddin,
- Palak Panchal,
- Matthew Riolo,
- Smit Shah,
- Afsar Barlas,
- Ke Xu,
- Lon Yin L. Chan,
- Alexandra Gruzinova,
- Sarah Kishinevsky,
- Lorenz Studer,
- Valentina Fossati,
- Scott A. Noggle,
- Julie R. White,
- Elisa de Stanchina,
- Sonia Sequeira,
- Kyle H. Anthoney,
- John W. Steele,
- Katia Manova-Todorova,
- Sujata Patil,
- Mark P. Dunphy,
- NagaVaraKishore Pillarsetty,
- Ana C. Pereira,
- Hediye Erdjument-Bromage,
- Thomas A. Neubert,
- Anna Rodina,
- Stephen D. Ginsberg,
- Natalia De Marco Garcia,
- Wenjie Luo,
- Gabriela Chiosis
Affiliations
- Maria Carmen Inda
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Suhasini Joshi
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Tai Wang
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Alexander Bolaender
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Srinivasa Gandu
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- John Koren III
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Alicia Yue Che
- Brain and Mind Research Institute, Weill Cornell Medical College
- Tony Taldone
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Pengrong Yan
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Weilin Sun
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Mohammad Uddin
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Palak Panchal
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Matthew Riolo
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Smit Shah
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Afsar Barlas
- Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
- Ke Xu
- Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
- Lon Yin L. Chan
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Alexandra Gruzinova
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Sarah Kishinevsky
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Lorenz Studer
- Department of Developmental Biology, Memorial Sloan Kettering Cancer Center
- Valentina Fossati
- The New York Stem Cell Foundation Research Institute
- Scott A. Noggle
- The New York Stem Cell Foundation Research Institute
- Julie R. White
- Comparative Pathology Laboratory, Memorial Sloan Kettering Cancer Center
- Elisa de Stanchina
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center
- Sonia Sequeira
- Office of Clinical Research, Memorial Sloan Kettering Cancer Center
- Kyle H. Anthoney
- Department of Biological Sciences, Humboldt State University
- John W. Steele
- Department of Biological Sciences, Humboldt State University
- Katia Manova-Todorova
- Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center
- Sujata Patil
- Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center
- Mark P. Dunphy
- Department of Radiology, Memorial Sloan Kettering Cancer Center
- NagaVaraKishore Pillarsetty
- Department of Radiology, Memorial Sloan Kettering Cancer Center
- Ana C. Pereira
- Department of Neuroscience, Rockefeller University
- Hediye Erdjument-Bromage
- Department of Cell Biology, NYU School of Medicine
- Thomas A. Neubert
- Department of Cell Biology, NYU School of Medicine
- Anna Rodina
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- Stephen D. Ginsberg
- Departments of Psychiatry, Neuroscience & Physiology & the NYU Neuroscience Institute, NYU School of Medicine
- Natalia De Marco Garcia
- Brain and Mind Research Institute, Weill Cornell Medical College
- Wenjie Luo
- Brain and Mind Research Institute, Weill Cornell Medical College
- Gabriela Chiosis
- Chemical Biology Program, Memorial Sloan Kettering Cancer Center
- DOI
- https://doi.org/10.1038/s41467-019-14082-5
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 19
Abstract
The biology of Alzheimer’s disease (AD) remains unknown. We propose AD is a protein connectivity-based dysfunction disorder whereby a switch of the chaperome into epichaperomes rewires proteome-wide connectivity, leading to brain circuitry malfunction that can be corrected by novel therapeutics.