Immunocytochemical localization of synphilin-1, an alpha-synuclein-associated protein, in neurodegenerative disorders.
Alpha-synuclein is a major component of Lewy bodies (LB) in Parkinson's disease (PD) and dementia with LB (DLB), as well as of glial cytoplasmic inclusions (GCI) in multiple system atrophy (MSA). Recently, a novel protein called synphilin-1 has been identified that associates with alpha-synuclein, and it has been reported that co-transfection of both alpha-synuclein and synphilin-1 in mammalian cells yielded eosinophilic cytoplasmic inclusions resembling LB. Immunocytochemical and ultrastructural investigations have now been performed on the brain of patients with various neurodegenerative disorders using anti-synphilin-1 antibodies. These antibodies immunostained the neuropil in a punctate pattern throughout the brain of control subjects. In PD, most LB observed in the brain stem were positive for synphilin-1. These LB showed intense staining in their central cores, but their peripheral portions were only weakly stained or unstained. Pale bodies and Lewy neurites, which were positive for alpha-synuclein, were synphilin-1 negative. In DLB, a small fraction of cortical LB were immunolabeled by anti-synphilin-1. In MSA, numerous GCI were positive for synphilin-1. Immunoelectron microscopy revealed that the reaction product was localized within filamentous and circular structures in LB. Various neuronal and glial inclusions in neurodegenerative disorders other than LB disease and MSA were synphilin-1 negative. These findings suggest that abnormal accumulation of synphilin-1 is specific for brain lesions in which alpha-synuclein is a major component.
Wakabayashi
Koichi
K
Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. koichi@cc.hirosaki-u.ac.jp
Engelender
Simone
S
Tanaka
Yuji
Y
Yoshimoto
Makoto
M
Mori
Fumiaki
F
Tsuji
Shoji
S
Ross
Christopher A
CA
Takahashi
Hitoshi
H
D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D016631:Lewy Bodies / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000276:immunology* / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051843:Synucleins; D051844:alpha-Synuclein
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C118958:SNCAIP protein, human; D051843:Synucleins; D051844:alpha-Synuclein