Involvement in alpha-synuclein function and pathology in lysosomal storage diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 25460500
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Yokohama City University
• Principal Investigator: YAMAGUCHI Akira 横浜市立大学, 医学研究科, 客員講師 (20381585)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: サンドホフ病 / ライソゾーム蓄積病 / GM2ガングリオシドーシス / α-シヌクレイン / オートファジー

Outline of Final Research Achievements

The accumulation of α-synuclein (ASyn) has been observed in several lysosomal storage diseases (LSDs) but it remains unclear if ASyn accumulation contributes to LSD pathology. ASyn also accumulates in the neurons of Sandhoff disease (SD) patients and SD model mice (Hexb-/- ASyn+/+ mice).
In this study, we explored the potential role of ASyn accumulation in the neurodegenerative process of LSDs, we generated Hexb-/- ASyn-/- mice. Here, we present evidence that autophagic and ubiquitin proteasome pathway are impaired, and mitochondrial function are damaged in Hexb-/- ASyn+/+ mice, but this improves in the absence of ASyn. However, this reducing ASyn accumulation is associated with little improvement in any clinical features of Hexb-/- ASyn+/+ mice.

Free Research Field

分子生物学