The role of synphilin-1 in synaptic function and protein degradation.
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.
Krüger
Rejko
R
Neurodegeneration Laboratory, Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. rejko.krueger@uni-tuebingen.de
D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C118958:SNCAIP protein, human