Molecular Mechanisms and Therapeutic Target of ALS/Asidan

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293202
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Okayama University
• Principal Investigator: Abe Koji 岡山大学, 医歯(薬)学総合研究科, 教授 (20212540)
• Co-Investigator(Kenkyū-buntansha): Yamashita Toru 岡山大学, 大学院医歯薬総合研究科脳神経内科学, 講師 (60644408) ; Ikeda Yoshio 岡山大学, 大学院医歯薬総合研究科脳神経内科学, 講師 (00282400)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 筋萎縮性側索硬化症 / Asidan / 運動ニューロン病 / NOP56 / iPS細胞

Outline of Final Research Achievements

We analyzed expression and distribution patterns of three RNA processing related proteins,nucleolar protein (NOP) 56 (identified as causative gene for Asidan), TDP-43, and FUS in lumbar and cervical cords of transgenic (Tg) SOD1 G93A ALS model mice. Tg mice showed progressive reduction of NOP56 levels in the large motor neurons from the early-symptomatic stage.TDP-43 and FUS protein levels showed a later decrease in the nucleus of large motor neuron at the end stage of the disease.
We also analyzed an autopsy sample from an Asidan patient. We found ubiquitin- and p62-positive inclusions in the cytoplasm of the inferior olivary nucleus of the Asidan patient,　(GGCCUG)n RNA foci in neuronal nucleiof the cerebellum, inferior olive, spinal cord. Of interest is that the giant RNA foci, nearly 10 lm in diameter, that were detected in Purkinje cells, spinal motor neurons and most frequently in the inferior olivary nucleus, may be responsible for pivotal clinical symptoms of Asidan.

Free Research Field

神経内科学