Is endoplasmic reticulum stress essential for motor neuron degeneration?

• 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
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• 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.

Research Products

• [Journal Article] Clinicopathological features of the first Asian family having vocal cord and pharyngeal weakness with distal myopathy due to a MATR3 mutation. (2015)
  • Author(s): Yamashita S, Mori A, Nishida Y, Kurisaki R, Tawara N, Nishikami T, Misumi Y, Ueyama H, Imamura S, Higuchi Y, Hashiguchi A, Higuchi I, Morishita S, Yoshimura J, Uchino M, Takashima H, Tsuji S, Ando Y.
  • Journal Title: Neuropathol Appl Neurobiol Volume: 41 Issue: 3 Pages: 391-398
  • DOI: 10.1111/nan.12179
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Muscle biopsy findings predictive of malignancy in rare infiltrative dermatomyositis (2013)
  • Author(s): Uchino M, Yamashita S, Uchino K, Mori A, Hara A, Suga T, Hirahara T, Koide T, Kimura E, Yamashita T, Ueda A, Kurisaki R, Suzuki J, Honda S, Maeda Y, Hirano T, Ando Y
  • Journal Title: Clin Neurol Neurosurg Volume: 115(5) Issue: 5 Pages: 603-6
  • DOI: 10.1016/j.clineuro.2012.07.019
  • Peer Reviewed