Is endoplasmic reticulum stress essential for motor neuron degeneration?

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860718
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kumamoto University
• Principal Investigator: Mori Akira 熊本大学, 医学部附属病院, 非常勤診療医師 (70608877)
• Co-Investigator(Renkei-kenkyūsha): ERA Takumi 熊本大学, 発生医学研究所, 教授 (00273706)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 筋萎縮性側索硬化症 / 小胞体ストレス / 運動ニューロン / TDP-43 / FUS

Outline of Final Research Achievements

We investigated whether endoplasmic reticulum (ER) stress is essential for motor neuron degeneration in both TDP-43 and FUS/TLS-aggregation models. In motor neurons differentiated from iPS cells derived from ALS patients, some molecules on ER stress pathways were upregulated in mutant FUS/TLS expressing cells. However, only a few molecules were upregulated commonly in all different types of mutant FUS/TLS cells. In TDP-43-aggregation model, it was suggested that sarcoplasmic TDP-43 aggregation induced ER stress and then provided tissue toxicity. In our observations, both FUS/TLS and TDP-43 aggregation might induce ER stress. Therefore, regulation of ER stress pathways would be a therapeutic target for amyotrophic lateral sclerosis.

Free Research Field

運動ニューロン疾患