Molecular mechanism underlying propagation of pathogenic protein aggregates in neurodegenerative disorders

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06588
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Keio University
• Principal Investigator: Eiichi Tokuda 慶應義塾大学, 理工学部(矢上), 助教 (00757510)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: 筋萎縮性側索硬化症 / タンパク質凝集体 / シーディング / 線虫

Outline of Final Research Achievements

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. The disease begins focally and spreads contiguously, resulting in progressive paralysis. The pathological hallmark of ALS is the accumulation of insoluble protein aggregates containing Cu/Zn-superoxide dismutase (SOD1) in motor neurons. The aim of this project was to clarify a molecular mechanism underlying the spread of lesion sites in the disease from the viewpoint of seeding activity of insoluble SOD1 aggregates. I first established two different methods: oral intake of E.coli forming the aggregates by thermoregulation, and exposure of the purified aggregates. Although transgenic C.elegans harboring human SOD1 were fed with the aggregates, feeding with either E.coli forming the aggregates or the purified aggregates did not induce the aggregation of human SOD1 in C.elegans. Furthermore, these aggregates did not affect overall lifespan and motor function of C.elegans.

Free Research Field

生化学、病態生理学