Significance of and treatment against galectin-3 and p22 accompanied with glial inflamation in ALS spinal cord

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07996
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Kyushu University
• Principal Investigator: HAYASHI SHINTARO 九州大学, 医学研究院, 共同研究員 (90312876)
• Co-Investigator(Kenkyū-buntansha): 山崎 亮 九州大学, 医学研究院, 准教授 (10467946) ; 小早川 優子 九州大学, 大学病院, 助教 (40733788)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 筋萎縮性側索硬化症 / グリア性炎症 / 脊髄前・側索 / 髄鞘淡明化 / 血液脳関門 / ELISA / 動物モデル

Outline of Final Research Achievements

The pathogenesis of amyotrophic lateral sclerosis (ALS) still remains to be elucidated, and the absence of distinct treatment is the matter to break through in this devasting disorder. After discovery of TDP-43 pathology, it is well known that degeneration of ALS spreads beyond the motor system, and among those areas, we have focused on the diffuse myelin pallor in the anterolateral funiculi outside the corticospinal tracts and massive microglia/macrophage infiltration in the corresponding region. These findings prompted us to examine involvement of activated microglia-associated molecules, galectin-3 and p22, by ELISA and proteome analyses, and to test if these two molecules are useful as early diagnostic marker and treatment targets of ALS. Presently, no significant results have been observed; however, during this study, several pitfalls for using ALS specimens and the ways how to minimize them are indicated, which might shed light on future studies sharing similar objectives.

Free Research Field

神経病理

Academic Significance and Societal Importance of the Research Achievements

ALSが最初に文献に記載され１世紀以上が経過しているものの、現在も病態は不明である。早期診断マーカーがない事実は、今後何らかの治療法が世に出たとしても患者は早期に治療を受ける機会を逸する事を意味する。今回私達は新しい視点でgalectin-3とp22という活性化ミクログリア関連分子に着目しALSの早期診断マーカーとしての有用性の検証と治療方法の樹立を試みた。残念ながら現段階で有意な結果を得られていないが、ELISA法やプロテオーム解析を用いた実験を行うにあたりALS検体特有のpit fallが示唆されたのでその改善策を考察し、今後同じ目的の研究が円滑に行われるための情報の一端を提供した。