Elevated levels of alpha-synuclein blunt cellular signal transduction downstream of Gq protein-coupled receptors

摘要: Alpha-synuclein is central to Parkinson's disease pathogenesis and pathology, however its precise functions are still unclear. It has been shown bind both PLCβ1 MAPKs, but how this property influences the downstream signaling of Gq protein-coupled receptors not elucidated. Here we show that recombinant expression alpha-synuclein in human neuroblastoma cells enhances cellular levels blunts pathway, preventing agonist-dependent rise cytoplasmic Ca2+. In addition, overexpressing abolishes activation ERK1/2 upon agonist stimulation, indicating an upstream action signal transduction pathway. This data demonstrates alpha-synuclein, when recombinantly expressed, interferes with normal Gq-protein coupled receptors, which then dysfunctional. Since many neurotransmitter systems utilize these receptor pathways mediate different abilities affected disease, argue novel perspective might be helpful designing treatment strategies for some non-motor symptoms synucleinopathies.