HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons.

作者: Patrick L. Heilman , SungWon Song , Carlos J. Miranda , Kathrin Meyer , Amit K. Srivastava

DOI: 10.1016/J.EXPNEUROL.2017.08.002

关键词:

摘要: Heat shock protein beta-1 (HSPB1), is a ubiquitously expressed, multifunctional chaperone. Mutations in HSPB1 result the development of late-onset, distal hereditary motor neuropathy type II (dHMN) and axonal Charcot-Marie Tooth disease with sensory involvement (CMT2F). The functional consequences mutations associated are unknown. also displays neuroprotective properties many neuronal models, including neuron amyotrophic lateral sclerosis (ALS). upregulated SOD1-ALS animal models during progression, predominately glial cells. Glial cells known to contribute loss ALS through non-cell autonomous mechanism. In this study, we examined role wild mutant an astrocyte-motor co-culture model system ALS. Astrocyte-specific overexpression was sufficient attenuate SOD1(G93A) astrocyte-mediated toxicity neurons, whereas, mutHSPB1 failed ameliorate toxicity. Expression phosphomimetic astrocytes reduced suggesting that phosphorylation may mediated-neuroprotection. These data provide evidence astrocytic expression play central health maintenance.

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