title: β-III Tubulin fragments inhibit α-synuclein accumulation in models of multiple system atrophy.
abstract: Multiple system atrophy (MSA) is a neurodegenerative disease caused by α-synuclein aggregation in oligodendrocytes and neurons. Using a transgenic mouse model overexpressing human α-synuclein in oligodendrocytes, we previously demonstrated that oligodendrocytic α-synuclein inclusions induce neuronal α-synuclein accumulation and progressive neuronal degeneration. α-Synuclein binds to β-III tubulin, leading to the neuronal accumulation of insoluble α-synuclein in an MSA mouse model. The present study demonstrates that α-synuclein co-localizes with β-III tubulin in the brain tissue from patients with MSA and MSA model transgenic mice as well as neurons cultured from these mice. Accumulation of insoluble α-synuclein in MSA mouse neurons was blocked by the peptide fragment β-III tubulin (residues 235-282). We have determined the α-synuclein-binding domain of β-III tubulin and demonstrated that a short fragment containing this domain can suppress α-synuclein accumulation in the primary cultured cells. Administration of a short α-synuclein-binding fragment of β-III tubulin may be a novel therapeutic strategy for MSA.
authors.affiliation: From the Laboratory of Research Resources, Research Institute, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu-shi, Aichi 474-8511, Japan and.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: From the Laboratory of Research Resources, Research Institute, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu-shi, Aichi 474-8511, Japan and.
authors.forename: Chenghua
authors.initials: C
authors.lastname: Jin
authors.affiliation: the Department of Neurology, Nagoya City Koseiin Medical Welfare Center, Aichi 465-8610, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Iwase
authors.affiliation: From the Laboratory of Research Resources, Research Institute, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu-shi, Aichi 474-8511, Japan and yazawaik@ncgg.go.jp.
authors.forename: Ikuru
authors.initials: I
authors.lastname: Yazawa
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D019578:Multiple System Atrophy / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D014404:Tubulin; D051844:alpha-Synuclein; C462941:beta3 tubulin, mouse
keywords: Multiple System Atrophy; Neurodegeneration; Protein Aggregation; Protein-Protein Interaction; Tubulin; alpha-Synuclein