Propagation of prion-like proteins and cellular responses

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H02356
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: HASEGAWA Masato 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 分野長 (10251232)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: タウ / αシヌクレイン / TDP-43 / 伝播

Outline of Final Research Achievements

We analyzed pathological tau in various neurodegenerative diseases and found that the C-terminal banding pattern of the insoluble tau is distinct for each disease, suggesting that the band patterns reflect different conformations of tau molecular species. We also showed that extracellular region of APP is involved in uptake of tau fibrils into cells, raising the possibility that APP influences cell-to-cell spreading of tau pathologies in AD. In addition, we identified that residues 274-353 are responsible for the conversion of TDP-43 to amyloid-like fibrils and that templated aggregation of TDP-43 by seeding with different peptides induces various types of TDP-43 pathologies. Regarding alpha-synuclein, we showed that fragmented amyloid-like aggregates of short alpha-synunclein fibrils are the key pathogenic seeds that trigger prion-like conversion, and that the propagation is recapitulated in wild-type marmoset by inoculation of sonicated mouse alpha-synculein fibrils.

Free Research Field

神経病理学