Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 468, Issue 4, Pages 677-683Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.11.015
Keywords
Spinal and bulbar muscular atrophy; Androgen receptor; Hepatocyte growth factor; Akt; Castration; Combination therapy
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [KAKENHI 18599002, 26293207]
- Japan Agency for Medical Research and Development, AMED [15ek0109048s0402]
- Grants-in-Aid for Scientific Research [26293207, 26670439, 26860665] Funding Source: KAKEN
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Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ)-encoding tract within the androgen receptor (AR) gene. The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs. Hepatocyte growth factor (HGF) is a polypeptide growth factor which has neuroprotective properties. To investigate whether HGF overexpression can affect disease progression in a mouse model of SBMA, we crossed SBMA transgenic model mice expressing an AR gene with an expanded CAG repeat with mice overexpressing HGF. Here, we report that high expression of HGF induces Akt phosphorylation and modestly ameliorated motor symptoms in an SBMA transgenic mouse model treated with or without castration. These findings suggest that HGF overexpression can provide a potential therapeutic avenue as a combination therapy with disease-modifying therapies in SBMA. (C) 2015 Elsevier Inc. All rights reserved.
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