Amyotrophic Lateral Sclerosis and TDP-43: Elucidation of molecular neuropathology in terms of spread from its beginning

2016 Fiscal Year Final Research Report

• Project/Area Number: 26250017
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Niigata University
• Principal Investigator: Takahashi Hitoshi 新潟大学, 脳研究所, 教授 (90206839)
• Co-Investigator(Kenkyū-buntansha): 小野寺 理 新潟大学, 脳研究所, 教授 (20303167) ; 豊島 靖子 新潟大学, 脳研究所, 准教授 (20334675) ; 他田 真理 新潟大学, 脳研究所, 助教 (30646394) ; 清水 宏 新潟大学, 脳研究所, 助教 (40608767)
• Co-Investigator(Renkei-kenkyūsha): KAKITA Akiyoshi 新潟大学, 脳研究所, 教授 (80281012) ; SAKIMURA Kenji 新潟大学, 脳研究所, 教授 (40162325) ; IKEUCHI Takeshi 新潟大学, 脳研究所, 教授 (20372469)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 筋萎縮性側索硬化症 / 神経病理学 / 脳神経疾患 / 神経変性疾患 / TDP-43

Outline of Final Research Achievements

We found that TDP-43 regulates the level of-its-own protein by alternative splicing within exon 6. Surprisingly, we found that the proportion of TDP-43 mRNA associated with this autoregulation increases in the spinal cord of ALS patients. It was confirmed that this mutant co-localized with TDP-43 immuno-positive inclusion body in anterior horn cells of ALS patients. This suggested that this abnormal protein may be the beginning of ALS lesion.
We reevaluated the cortical TDP-43 pathology in cases of sporadic ALS, using semi-quantitative estimation of pTDP-43-positive dystrophic neurite in the temporal neocortex,the case were divided into three groups, types 1, 2a and 2b. Type 2b has characteristic clinicopathological features. Considering the patient survaival time and severity of motor neuron loss, each group was regarded as independent subtype, indicating that transition from type 1 to type 2a, or from type 2a to type 2b during the disease course appeared unlikely.

Free Research Field

神経病理学