کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5629086 1580142 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research PaperHSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Research PaperHSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons
چکیده انگلیسی


- Overexpression of HSPB1 in astrocytes attenuates astrocyte-mediated motor neuron toxicity.
- Phosphorylation contributes to HSPB1-mediated non-cell autonomous neuroprotection.
- Axonal neuropathy-associated HSPB1 mutations result in loss of astrocyte-mediated motor neuron toxicity.

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

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 297, November 2017, Pages 101-109
نویسندگان
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