TY - JOUR
T1 - Immunocytochemical localization of synphilin-1, an α-synuclein-associated protein, in neurodegenerative disorders
AU - Wakabayashi, Koichi
AU - Engelender, Simone
AU - Tanaka, Yuji
AU - Yoshimoto, Makoto
AU - Mori, Fumiaki
AU - Tsuji, Shoji
AU - Ross, Christopher A.
AU - Takahashi, Hitoshi
N1 - Funding Information:
Acknowledgements We would like to thank Mr. S. Egawa, Mr. T. Hasegawa, Ms. C. Tanda, Ms. Y. Ohta and Ms. J. Takasaki for their technical assistance, and Ms. M. Machida and Ms. K. Abe for their help in preparing the manuscript. This work was supported by NIH grants NS 38377 and NS 16375, a research grant from the Research Committee for CNS Degenerative Diseases from the Ministry of Health and Welfare, Japan, and Grants-in-Aid for Exploratory Research from the Ministry of Education, Science, Sports and Culture, Japan.
PY - 2002
Y1 - 2002
N2 - α-Synuclein 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 α-synuclein, and it has been reported that co-transfection of both α-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 α-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 α-synuclein is a major component.
AB - α-Synuclein 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 α-synuclein, and it has been reported that co-transfection of both α-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 α-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 α-synuclein is a major component.
KW - Glial cytoplasmic inclusion
KW - Lewy body
KW - Multiple system atrophy
KW - Synphilin-1
KW - α-Synuclein
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U2 - 10.1007/s004010100451
DO - 10.1007/s004010100451
M3 - Review article
C2 - 11907799
AN - SCOPUS:0036938071
SN - 0001-6322
VL - 103
SP - 209
EP - 214
JO - Acta neuropathologica
JF - Acta neuropathologica
IS - 3
ER -