TY - JOUR T1 - Chaperones in Neurodegeneration JF - The Journal of Neuroscience JO - J. Neurosci. SP - 13853 LP - 13859 DO - 10.1523/JNEUROSCI.2600-15.2015 VL - 35 IS - 41 AU - Iris Lindberg AU - James Shorter AU - R. Luke Wiseman AU - Fabrizio Chiti AU - Chad A. Dickey AU - Pamela J. McLean Y1 - 2015/10/14 UR - http://www.jneurosci.org/content/35/41/13853.abstract N2 - 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. ER -