Identification and characterization of cell-to-cell transmissible alpha-synuclein seed

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K21283
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology; General anatomy (including histology/embryology)
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Katsutoshi Taguchi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (60462701)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: α-Synuclein / prion-like propagation / seed / Parkinson's disease

Outline of Final Research Achievements

α-Synuclein (αSyn) is one of major components of Lewy bodies and Lewy Neurites, the well-known pathological hallmarks of synucleinopathies including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). According to recent studies, cell-to-cell transmission of pathological αSyn in the brain is critical event for neurodegeneration. However, biochemical properties of these pathological molecules remain to be elucidated. Here, we isolated some characteristic αSyn-oligomers derived from preformed fibrils of αSyn. Next, we further recovered extracellular αSyn-oligomers having an uniform molecular mass in Native-PAGE from pathogenic conditioned culture medium. These oligomers successfully induced LB-pathology in cultured hippocampal neurons. Now, we are characterizing the pathogenic species of αSyn. These molecules will be a better target to inhibit the disease propagation via cell-to-cell transmission in PD and DLB.

Free Research Field

神経解剖学