title: Pioglitazone suppresses neuronal and muscular degeneration caused by polyglutamine-expanded androgen receptors.
abstract: Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by the expansion of a CAG repeat in the androgen receptor (AR) gene. Mutant AR has been postulated to alter the expression of genes important for mitochondrial function and induce mitochondrial dysfunction. Here, we show that the expression levels of peroxisome proliferator-activated receptor-γ (PPARγ), a key regulator of mitochondrial biogenesis, were decreased in mouse and cellular models of SBMA. Treatment with pioglitazone (PG), an activator of PPARγ, improved the viability of the cellular model of SBMA. The oral administration of PG also improved the behavioral and histopathological phenotypes of the transgenic mice. Furthermore, immunohistochemical and biochemical analyses demonstrated that the administration of PG suppressed oxidative stress, nuclear factor-κB (NFκB) signal activation and inflammation both in the spinal cords and skeletal muscles of the SBMA mice. These findings suggest that PG is a promising candidate for the treatment of SBMA.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Iida
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan ka2no@med.nagoya-u.ac.jp sobueg@med.nagoya-u.ac.jp.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakatsuji
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Adachi
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Genki
authors.initials: G
authors.lastname: Tohnai
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ikenaka
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Speech Pathology and Audiology, Aichi-Gakuin University School of Health Science, Nisshin, Aichi 470-0195, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan and Kishida Clinic, Toyonaka, Osaka 560-0021, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kishida
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan ka2no@med.nagoya-u.ac.jp sobueg@med.nagoya-u.ac.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D020966:Muscular Disorders, Atrophic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage*; D019680:Trinucleotide Repeat Expansion / Q000187:drug effects
chemical_list: D010455:Peptides; D047492:Peroxisome Proliferator-Activated Receptors; D011944:Receptors, Androgen; D045162:Thiazolidinediones; C097188:polyglutamine; D000077205:Pioglitazone