Elucidation of molecular mechanisms of defective neuromuscular signal transmission as a primary cause of sarcopenia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22802
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Nagoya University
• Principal Investigator: Ohno Kinji 名古屋大学, 医学系研究科, 教授 (80397455)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: サルコペニア / 廃用性筋萎縮 / 神経筋接合部 / リボタグマウス / 遺伝子発現プロファイル

Outline of Final Research Achievements

Accumulating knowledge points to the notion that defects in the neuromuscular signal transmission are potentially the primary cause of amyotrophy including sarcopenia and muscle disuse atrophy. To explore NMJ-specific genes that are responsible for sarcopenia, we performed extensive gene expression profiling of the mouse motor endplate using RiboTag mouse that enables Cre-mediated HA-tagging to a ribosomal protein, RPL22. Analysis of genes expressed at the motor endplate showed that the phosphatidylinositol signaling system and the extracellular matrix receptor interaction, the roles of which at the neuromuscular junction remain to be elucidated, were highly expressed at the motor endplate. Analysis of subsets of these gene sets further revealed that diacylglycerol kinases, phosphatidylinositol kinases, phospholipases, integrins, laminins were enriched at the motor endplate.

Free Research Field

神経遺伝情報学分野

Academic Significance and Societal Importance of the Research Achievements

サルコペニアは世界で男女とも10%の有病率と推定されており高齢者のフレイルの最大要因となっている。しかし、サルコペニアは対症療法以外の薬物療法が存在しない「一般的な病気（common disease）」の代表疾患になっている。近年、サルコペニアに認められる神経筋接合部信号伝達障害はサルコペニアに伴う二次的な現象ではなくサルコペニアの一次的な原因の可能性が指摘されてきた。サルコペニアにともなう神経筋接合部の信号伝達障害の病態を明らかにすることによりサルコペニアの新規治療法開発につながることが期待される。