title: Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration.
abstract: 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.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Department of Neurology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555, Japan. Electronic address: hadachi-ns@umin.org.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Adachi
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Department of Neurology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555, Japan.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Iida
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Genki
authors.initials: G
authors.lastname: Tohnai
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakatsuji
authors.affiliation: Center for Advanced Research and Education, Asahikawa Medical University, 1-1-1- Higashinijo Midorigaoka, Asahikawa 078-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Funakoshi
authors.affiliation: Neurogen Inc., 1-1-52-201 Nakahozumi, Ibaraki 567-0034, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: sobueg@med.nagoya-u.ac.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000818:Animals; D002369:Castration / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020966:Muscular Disorders, Atrophic / Q000378:metabolism* / Q000628:therapy*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: C553307:HGF protein, mouse; D017228:Hepatocyte Growth Factor
keywords: Akt; Androgen receptor; Castration; Combination therapy; Hepatocyte growth factor; Spinal and bulbar muscular atrophy