The mechanism of neuronal cell death induced by a new mutation of peroxisomal enzyme via the mitochondorial disfunction

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893162
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Hiroshima University
• Principal Investigator: Matsuda Yukiko 広島大学, 原爆放射線医科学研究所, 研究員 (10735301)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: ペルオキシソーム / 脊髄小脳変性症 / 脂肪酸代謝

Outline of Final Research Achievements

A novel causative gene of SCD, HSD17B4, whose mutation was newly identified by exome analysis of SCD patients, was analyzed using patient-derived fibroblasts. HSD17B4 encodes the DBP enzyme, which requires proteolysis and multimerization to be functional. The mutation decreased the proteolytically processed fragment of DBP in the patient fibroblasts. The amount of VLCFA, a DBP substrate, in serum did not show significant change, and the accumulation of intracellular lipids was not detected. We generated iPSCs from the patient-derived fibroblasts. We will further analyze SCD pathogenesis using neuronally differentiated iPS.

Free Research Field

神経科学