Effect of lysosomal enzymes on alpha-synuclein accumulation causing neurodegeneration

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06764
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: Suzuki Yasuyo 愛知県心身障害者コロニー発達障害研究所, 遺伝学部, 研究員 (60416188)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: α-synuclein / パーキンソン病 / リソソーム / カテプシン / β-グルコセレブロシダーゼ

Outline of Final Research Achievements

α-Synuclein is a 140-amino acid protein and abundant in presynaptic terminals of neurons. Intracellular aggregation of α-synuclein is a pathological feature of neurodegenerative diseases, such as Parkinson’s disease (PD). Lysosomal dysfunction and α-synuclein accumulation are considered as the major pathogenic features in PD. For instance, mutations in β-glucocerebrosidase (GBA) gene, responsible for Gaucher disease, are known as a risk factor for PD. Recent studies demonstrate that deficiency of lysosomal enzymes causes lysosomal dysfunction and α-synuclein accumulation; however, the molecular mechanism of α-synuclein accumulation remains unclear. In this study, we investigated the effects of reduced activity of lysosomal enzymes GBA and cathepsins B and D on α-synuclein accumulation. Our study suggested that dysfunctions of cathepsins B and D are more critical role in accumulation and insolubilization of α-synuclein than the GBA dysfunction.

Free Research Field

生化学