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J Neurosci. 2015 Oct 14;35(41):13853-9. doi: 10.1523/JNEUROSCI.2600-15.2015.

Chaperones in Neurodegeneration.

Author information

1
University of Maryland School of Medicine, Baltimore, Maryland 21201, ilindberg@som.umaryland.edu.
2
University of Pennsylvania, Philadelphia, Pennsylvania 19104.
3
The Scripps Research Institute, La Jolla, California 92037.
4
University of Florence, 50121 Florence, Italy.
5
University of South Florida, Tampa, Florida 33620, and.
6
Mayo Clinic, Jacksonville, Florida 32224.

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.

SIGNIFICANCE STATEMENT:

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.

KEYWORDS:

Parkinson's disease; chaperone; heat shock proteins; neurodegeneration; protein misfolding; proteostasis

PMID:
26468185
PMCID:
PMC4604223
DOI:
10.1523/JNEUROSCI.2600-15.2015
[Indexed for MEDLINE]
Free PMC Article

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