The neuronal dysfunction by alpha-synuclein oligomers in Parkinson's disease

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461287
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Department of Clinical Research, National Hospital Organization Utano National Hospital
• Principal Investigator: Yamamoto Kenji 独立行政法人国立病院機構(宇多野病院臨床研究部), その他部局等, 研究員(移行) (50378775)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: αシヌクレイン / パーキンソン病 / レビー小体型認知症 / IP3受容体 / カルシウム遊離 / カルシウム結合蛋白 / オリゴマー / カルシウムチャンネル

Outline of Final Research Achievements

α-Synuclein oligomers and dysregulated activity-dependent Ca2+ homeostasis play pivotal roles in the selective neuronal damage occurring in Lewy body disease. The current study used electrophysiological and immunochemical analyses to evaluate how intracellular α-synuclein oligomers act on the neuronal excitability and Ca2+ dynamics in neocortical pyramidal neurons. Intracellularly applied higher-order α-synuclein oligomers directly capture calcium-binding protein 1, a negative regulator of inositol trisphosphate receptor (IP3R) gating, and cause the aberrant form of Ca2+-induced Ca2+ release from IP3R during multiple spikes. This is a non- physiological action in neocortical neurons and is blocked by L-type Ca2+ channel blockers. This oligomeric α-synuclein-mediated mechanism may cause intracellular Ca2+ dysregulation and could be the molecular basis for neuronal vulnerability in Lewy body disease.

Free Research Field

神経内科学