α-Synuclein, synphilin-1 and inclusion body formation in α-synucleinopathies

Abstract

α-Synuclein (αS), originally identified as a presynaptic protein, is now known to be a major component of Lewy bodies (LBs) in Parkinson’s disease (PD) and dementia with LBs (DLB), as well as of glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA). Recently, a novel protein called synphilin-1 has been identified that associates with αS, and it has been reported that co-transfection of both αS and synphilin-1 in mammalian cells yielded eosinophilic cytoplasmic inclusions resembling LBs. We performed immunohistochemical investigations on the brains of patients with various neurodegenerative disorders using antibodies against synphilin-1. The antibodies immunostained the neuropil in a punctate pattern throughout the brains of control subjects that resembles the pattern for αS. In PD and DLB, most LBs observed in the brainstem and a small fraction of cortical LBs were immunolabeled by anti-synphilin-1. In MSA, almost all the GCIs were positive for synphilin-1. Various neuronal and glial inclusions in neurodegenerative disorders other than LB disorders and MSA were synphilin-1-negative. These findings suggest that abnormal accumulation of synphilin-1 is specific for α-synucleinopathy lesions.