title: Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy.
abstract: Glial cytoplasmic inclusions (GCIs) are the histological hallmark of multiple system atrophy (MSA). In six postmortem brains of patients with MSA, 14-3-3-protein immunoreactivity was identified in GCIs predominately in the white matter tissue of the basal forebrain and cerebellum. Using double immunohistochemistry, co-localization of 14-3-3-protein and alpha-synuclein immunoreactivities in the GCIs was confirmed. The immunolabeling rate of GCIs with 14-3-3 proteins varied regionally from approximately 40% to 90%. Semiquantitative analysis yielded a significant negative correlation between degree of tissue degeneration and density of 14-3-3-protein-immunoreactive GCIs. The 14-3-3 proteins are active cofactors involved in cellular regulation through binding to phosphorylated motifs in target proteins and alpha-synuclein is a known target of 14-3-3. Our study suggests that 14-3-3 proteins are closely associated with alpha-synuclein in GCIs and 14-3-3 proteins may be candidate cofactors of alpha-synuclein in GCI formation.
authors.affiliation: Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu City, 183-8526 Tokyo, Japan. komori@tmin.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Komori
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Arai
authors.forename: Takanori
authors.initials: T
authors.lastname: Hirose
authors.forename: Toshio
authors.initials: T
authors.lastname: Mizutani
authors.forename: Masaya
authors.initials: M
authors.lastname: Oda
mesh_terms: D048948:14-3-3 Proteins; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D051843:Synucleins; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D051844:alpha-Synuclein
chemical_list: D048948:14-3-3 Proteins; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase