Misfold protein removal therapy with CCR2-positive cells from peripheral nerves in motor neuron disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07963
• 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: Yamasaki Ryo 九州大学, 医学研究院, 准教授 (10467946)
• Co-Investigator(Kenkyū-buntansha): 山口 浩雄 九州大学, 大学病院, 特任講師 (00701830) ; 藤井 敬之 九州大学, 医学研究院, 助教 (30822481) ; 立石 貴久 久留米大学, 医学部, 講師 (50423546) ; 緒方 英紀 九州大学, 大学病院, 助教 (90778838)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 筋萎縮性側索硬化症 / マクロファージ / 末梢神経 / 異常蛋白 / モデルマウス / 変異SOD1 / CCR2

Outline of Final Research Achievements

Amyotrophic lateral sclerosis is an intractable disease in which brain and spinal cord motor neurons are selectively shed. Muscle atrophy of the whole body progresses, leading to limb paralysis and respiratory failure 2-3 years after the onset. The disease mechanism is unknown, and there is no effective treatment. We focused on phagocytic cells (macrophages) that infiltrate the peripheral nerves of patients and disease model mice and used genetically modified animals to determine whether these cells are neuroprotective or harmful. We investigated the effects of blocking macrophage infiltration into the peripheral nerves. As a result, the model mice in which phagocytic cell infiltration was suppressed had a shorter lifespan than usual, and neuronal loss also progressed. In other words, we found for the first time that phagocytic cells infiltrating peripheral nerves are disease-protective.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

筋萎縮性側索硬化症は脳と脊髄の病気と考えられ、末梢神経はこれまで注目されていなかった。末梢神経に浸潤する貪食細胞の疾患病態への関与についても全く不明であった。今回の研究で、末梢神経に浸潤する貪食細胞が異常蛋白を除去する作用を介して中枢神経(脊髄の運動神経)細胞を保護することがわかった。この仕組はこれまで解明されておらず、画期的な発見であった。