Molecular chaperones and neuronal proteostasis.

Heather L Smith, Wenwen Li, Michael E Cheetham

Seminars in cell & developmental biology 2015 Apr

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Protein homeostasis (proteostasis) is essential for maintaining the functionality of the proteome. The disruption of proteostasis, due to genetic mutations or an age-related decline, leads to aberrantly folded proteins that typically lose their function. The accumulation of misfolded and aggregated protein is also cytotoxic and has been implicated in the pathogenesis of neurodegenerative diseases. Neurons have developed an intrinsic protein quality control network, of which molecular chaperones are an essential component. Molecular chaperones function to promote efficient folding and target misfolded proteins for refolding or degradation. Increasing molecular chaperone expression can suppress protein aggregation and toxicity in numerous models of neurodegenerative disease; therefore, molecular chaperones are considered exciting therapeutic targets. Furthermore, mutations in several chaperones cause inherited neurodegenerative diseases. In this review, we focus on the importance of molecular chaperones in neurodegenerative diseases, and discuss the advances in understanding their protective mechanisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Citation

Heather L Smith, Wenwen Li, Michael E Cheetham. Molecular chaperones and neuronal proteostasis. Seminars in cell & developmental biology. 2015 Apr;40:142-52