Immunocytochemical localization of synphilin-1, an alpha-synuclein-associated protein, in neurodegenerative disorders

Acta Neuropathologica
K WakabayashiHitoshi Takahashi

Abstract

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 lo...Continue Reading

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