Molecular bases of selective vulnerability of motor neurons in amyotrophic lateral sclerosis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15081
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Tanabe Yasuto 京都大学, 医学研究科, 客員研究員 (10311309)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 神経変性疾患

Outline of Final Research Achievements

Neurodegenerative diseases can be characterized by their unique distinct set of neuronal subtypes that exhibit progressive and selective vulnerability. In ALS, progressive and selective degeneration with the accumulation of pathological aggregates, including TDP-43, is observed in motor neurons (MNs), especially those that innervate fast muscles (FF-MN) in the spinal cord. Our study using cultured cells in vitro showed that Notch signals involved in the specification of FF-MN appeared to be also involved in the acquisition of vulnerability against TDP-43 full-length protein expression and resulted in the formation TDP-43 aggregates mostly located within the nucleus.　Although we were not able to show cytoplasmic re-distribution of TDP-43 aggregates even in the presence of a proteasome inhibitor, our results may add to the emerging view that nuclear TDP-43 proteinopathy may take place prior to the onset of cytoplasmic event and underlie the selective vulnerability of MNs in ALS.

Free Research Field

神経病理　神経発生