title: Chaperones in Neurodegeneration.
abstract: Cellular protein homeostasis (proteostasis) maintains the integrity of the proteome and includes protein synthesis, folding, oligomerization, and turnover; chaperone proteins assist with all of these processes. Neurons appear to be especially susceptible to failures in proteostasis, and this is now increasingly recognized as a major origin of neurodegenerative disease. This review, based on a mini-symposium presented at the 2015 Society for Neuroscience meeting, describes new work in the area of neuronal proteostasis, with a specific focus on the roles and therapeutic uses of protein chaperones. We first present a brief review of protein misfolding and aggregation in neurodegenerative disease. We then discuss different aspects of chaperone control of neuronal proteostasis on topics ranging from chaperone engineering, to chaperone-mediated blockade of protein oligomerization and cytotoxicity, to the potential rescue of neurodegenerative processes using modified chaperone proteins.
  
  
  CONCLUSIONS
  Aberrant protein homeostasis within neurons results in protein misfolding and aggregation. In this review, we discuss specific roles for protein chaperones in the oligomerization, assembly, and disaggregation of proteins known to be abnormally folded in neurodegenerative disease. Collectively, our goal is to identify therapeutic mechanisms to reduce the cellular toxicity of abnormal aggregates.
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland 21201, ilindberg@som.umaryland.edu.
authors.forename: Iris
authors.initials: I
authors.lastname: Lindberg
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: James
authors.initials: J
authors.lastname: Shorter
authors.affiliation: The Scripps Research Institute, La Jolla, California 92037.
authors.forename: R Luke
authors.initials: RL
authors.lastname: Wiseman
authors.affiliation: University of Florence, 50121 Florence, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Chiti
authors.affiliation: University of South Florida, Tampa, Florida 33620, and.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Dickey
authors.affiliation: Mayo Clinic, Jacksonville, Florida 32224.
authors.forename: Pamela J
authors.identifier: http://orcid.org/0000-0003-4870-5715
authors.initials: PJ
authors.lastname: McLean
mesh_terms: D000818:Animals; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones
keywords: Parkinson's disease; chaperone; heat shock proteins; neurodegeneration; protein misfolding; proteostasis