Development of a Novel Therapeutic Approach Focusing on Polarity Conversion of Reactive Astrocytes in ALS

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16572
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Tohoku University
• Principal Investigator: Shijo Tomomi 東北大学, 大学病院, 医員 (50836898)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ALS / SOD1 / astrocyte / fibromodulin

Outline of Final Research Achievements

Amyotrophic lateral sclerosis (amyotrophic lateral sclerosis, ALS) is known to cause non-cell-autonomous neuropathy by glial cells such as astrocytes and microglia. Reactive astrocytes have either cytotoxic (A1) or protective (A2) aspects. In this study, we first analyzed the reactive pattern of astrocytes in ALS animal models in order to develop a novel treatment for ALS focusing on the polarity shift of reactive astrocytes. Cytotoxic A1marker expression was predominantly increased in early-onset ALS animal models, which was useful to consider the timing of intervention. Furthermore, we divided rats into forelimb- and hindlimb-onset groups and performed RNA sequencing in the cervical and lumbar spinal cords to identify a novel gene, Fmod, that may be involved in the pathogenesis and development of the disease.

Free Research Field

neurology

Academic Significance and Societal Importance of the Research Achievements

ALSの発症早期において細胞障害性のアストロサイトが優位に活性化していることが明らかとなり、アストロサイトの極性転換を狙った新規治療法を実施する時期の検討に有用と考えられる。さらに発症部位特異的に発現が亢進していた遺伝子FmodはALSの発症や病態進展に関与している可能性があると考えられ、今後の解析が重要である。