| Institution: | 1. Department of Pharmacology, Peripheral Neuropathy Research Center (PNRC), Dong-A University College of Medicine, Busan, 49201, South Korea;2. Department of Biochemistry, Peripheral Neuropathy Research Center (PNRC), Dong-A University College of Medicine, Busan, 49201, South Korea;3. Department of Neurology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea;1. Department of Biochemistry, School of Biology, Moscow State University, Moscow 119991, Russian Federation;2. Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium;1. Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea;2. Division of Tumor Immunology, National Cancer Center, Goyang, 10408, South Korea;3. Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine, Incheon, 22212, South Korea;1. Department of Periodontics, Shenyang Stomatological hospital, Shenyang, Liaoning, People’s Republic of China;2. Department of Oral Surgery, Shenyang Stomatological hospital, Shenyang, Liaoning, People’s Republic of China;3. Department of Pediatric Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China;1. Flaum Eye Institute, USA;2. Department of Medicine, University of Rochester, Rochester, NY, USA |
| Abstract: | Distal hereditary motor neuropathies (dHMN) are a group of inherited peripheral nerve disorders characterized by length-dependent motor neuron weakness and subsequent muscle atrophy. Missense mutations in the gene encoding small heat shock protein HSPB1 (HSP27) have been associated with hereditary neuropathies including dHMN. HSPB1 is a member of the small heat shock protein (sHSP) family characterized by a highly conserved α-crystallin domain that is critical to their chaperone activity. In this study, we modeled HSPB1 mutant-induced neuropathies in Drosophila using a human HSPB1S135F mutant that has a missense mutation in its α-crystallin domain. Overexpression of the HSPB1 mutant produced no significant defect in the Drosophila development, however, a partial reduction in the life span was observed. Further, the HSPB1 mutant gene induced an obvious loss of motor activity when expressed in Drosophila neurons. Moreover, suppression of histone deacetylase 6 (HDAC6) expression, which has critical roles in HSPB1 mutant-induced axonal defects, successfully rescued the motor defects in the HSPB1 mutant Drosophila model. |
