The association between alpha-synuclein and SOCE mechanism in cellular models of Parkinson's disease.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870441
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology; Neurochemistry/Neuropharmacology
• Research Institution: Tottori University
• Principal Investigator: ITO Satoru 鳥取大学, 医学部附属病院, 助教 (20448195)
• Research Collaborator: NAKASO Kazuhiro ; NAKASHIMA Kenji
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: パーキンソン病 / 小胞体 / TRPC1チャネル / カルシウムチャネル / モデル細胞 / PC12細胞 / ミトコンドリア毒性 / SOCE機構

Outline of Final Research Achievements

The endogenous store-operated calcium entry (SOCE) mechanism via TRPC1 channel is important to the maintenance of endoplasmic reticulum function. In recent years, a decreased expression level of TRPC1 was shown in the autopsied brain of Parkinson's disease (PD) patients. In addition, α-synuclein (AS) is also known to have cytotoxicity to the dopaminergic cells in PD.
We investigated the association between SOCE mechanism and AS pathology. We constructed PC12 cell line which overexpressed human AS. The expression level of TRPC1 was decreased by stimulation of mitochondrial stressors. Overexpression of human α-synuclein did not affect the TRPC1 suppression seen in mitochondrial stressor exposures. Meanwhile, TRPC1 inhibitor increased α-synuclein cytotoxicity.
According to these results, it is considered that mitochondrial stressors causes dysfunction of SOCE by inhibition of TRPC1 expression, and TRPC1 inhibition may lead to enhance the α-synuclein cytotoxicity.

Free Research Field

神経内科学、神経分子生物学