AbstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive and fatal loss of muscle strength, driven by the degeneration of motor neurons—nerve cells that transmit motor commands from the brain to muscles. A hallmark of ALS is that large and strong body movements are affected first, which is attributed to the fact that large motor neurons responsible for powerful muscle contractions are more vulnerable to degeneration. However, the mechanisms underlying the size-dependent susceptibility of motor neurons in ALS remain largely unknown. Clarifying these mechanisms is expected not only to deepen our understanding of ALS pathology but also to provide insights for developing effective therapeutic strategies.はじめに筋萎縮性側索硬化症（ALS）は，脳からの運動指令を筋肉に伝達する神経細胞「運動ニューロン」大学共同利用機関法人情報・システム研究機構国立遺伝学研究所遺伝形質研究系神経システム病態研究室・准教授National Institute of Genetics浅川 和秀Kazuhide Asakawa― 29 ―This study explores motor neuron vulnerability in ALS from a novel perspective: differences in their ability to respond to DNA damage, based on the general property of neurons wherein neural activity can induce such damage. To visualize DNA damage response in vivo, we generated a transgenic zebrafish line expressing a potential DNA damage marker protein in spinal motor neurons. This approach leverages the high tissue transparency of zebrafish larvae, enabling live imaging of spinal cord neurons. Furthermore, we compared the behavior of the marker protein in spinal motor neurons between wild-type larvae and those lacking the tardbp/TARDBP gene, which encodes the ALS-associated protein TDP-43. Our results reveal a unique property of the marker protein in spinal motor neurons under TDP-43-deficient conditions.DNA 損傷応答能の低下がもたらす神経細胞の ALS 脆弱性The…role…of…DNA…damage…response…deficiencyin…ALS-related…neuronal…susceptibility
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