, Volume 318, Issue 1, pp 195-199
Date: 19 Aug 2004

The role of synphilin-1 in synaptic function and protein degradation

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Abstract

The name synphilin-1 comes from its identification as an alpha-synuclein-interacting protein (SNCAIP) in yeast two-hybrid screens. Since alpha-synuclein (PARK1) was the first gene identified as causing inherited forms of Parkinson’s disease (PD), synphilin-1 was quickly implicated in neurodegeneration in PD. Recently, the first genetic evidence for the direct contribution of synphilin-1 in the pathogenesis of PD has been defined with the identification of an R621C mutation as a susceptibility factor for PD in two German patients. Extensive in vitro studies have determined the physiological functions of synphilin-1, identified novel synphilin-1-interacting proteins, and linked synphilin-1 to ubiquitin-mediated protein degradation. The present article provides an overview of the current concepts of the role of synphilin-1 in synaptic function and protein degradation and in the molecular mechanisms leading to neurodegeneration in PD.

The work of R.K. on synphilin-1 is supported by a grant from the Fritz Thyssen Foundation, a grant from the Federal Ministry of Education and Research (Fö 01KS9602), and the Interdisciplinary Center of Clinical Research Tübingen (IZKF)