Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy.
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.
Komori
Takashi
T
Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu City, 183-8526 Tokyo, Japan. komori@tmin.ac.jp
Ishizawa
Keisuke
K
Arai
Nobutaka
N
Hirose
Takanori
T
Mizutani
Toshio
T
Oda
Masaya
M
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
D048948:14-3-3 Proteins; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase