title: XIAP immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy.
abstract: X-linked inhibitor of apoptosis protein (XIAP) selectively binds to caspases-3, -7 and -9, and inhibits the activities of these caspases. To elucidate the role of XIAP in patients with multiple system atrophy (MSA), we performed immunohistochemical studies on XIAP in formalin-fixed, paraffin-embedded sections from 8 normal subjects and 10 patients with MSA. In normal brains, several types of neurons were immunostained for XIAP, and XIAP-immunopositive oligodendrocytes were scattered throughout the cerebral and cerebellar white matter. In the MSA brains, neuronal XIAP immunoreactivity was spared even in the severely-affected lesions, and glial cytoplasmic inclusions (GCIs), neuronal cytoplasmic inclusions (NCIs) and dystrophic neurites were all intensely immunoreactive for XIAP. A semiquantitative analysis of mid-pons sections double-immunostained for XIAP and α-synuclein demonstrated that the average percentages of XIAP-immunopositive GCIs and NCIs in the pontine nucleus were 70.2% and 82.2%, respectively. Our results suggest that a widespread accumulation of XIAP may occur in brains with MSA, and that XIAP may be partially associated with the pathogenesis of MSA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawamoto
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Ito
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism; D019578:Multiple System Atrophy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D012697:Serine Endopeptidases / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D012697:Serine Endopeptidases; D000074923:High-Temperature Requirement A Serine Peptidase 2