Talk abstracts
Talk on Tuesday 04:45-05:00pm submitted by Patrick Heilman
HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons in vitro
Patrick L. Heilman (Department of Biological Chemistry and Pharmacology), SungWon Song (Nationwide Childrens Hospital), Carlos J. Miranda (Nationwide Childrens Hospital), Kathrin Meyer (Nationwide Childrens Hospital), Amit K. Srivastava (Department of Pediatrics Surgery), Christopher G. Wier (Department of Biological Chemistry and Pharmacology)
Abstract:
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 fails to ameliorate motor neuron toxicity. Expression of a phosphomimetic HSPB1 mutant in SOD1(G93A) astrocytes also reduced toxicity to motor neurons, suggesting HSPB1 mediated-neuroprotection may be phosphorylation dependent. These data provide evidence that astrocytic HSPB1 expression may play a central role in motor neuron health and maintenance.
Keywords: HSPB1, Motor Neuropathy