える影響をより精緻に描き出す必要がある．これらの研究は，ALS や前頭側頭型認知症（FTD）など TDP-43 関連神経変性疾患の病態解明と，治療標的の探索に向けた基盤情報を提供することが期待される．謝 辞本研究は，公益財団法人 中外創薬科学財団からの助成金の支援を受けて実施されました．中外創薬科学財団に深く感謝いたします．また，研究を支援してくださった，国立遺伝学研究所神経システム病態研究室メンバーの皆さん，国立遺伝学研究所発生遺伝学研究室，川上浩一教授，および，川上研究室メンバーの皆さんに，深く感謝いたします．引用文献…1. Asakawa K, Handa H, Kawakami K. Optogenetic modulation of TDP-43 oligomerization accelerates ALS-related pathologies in the spinal motor neurons. Nature Communications, 11: 1004 (2020).2. Asakawa K, Suster M, Mizusawa K, Nagayoshi S, Kotani T, Urasaki A, Kishimoto Y, Hibi M, Kawakami K. Genetic dissection of neural circuits by Tol2 transposon-mediated Gal4 gene and enhancer trapping in zebrafish. Proc Natl Acad Sci USA, 105:1255-60 (2008).3. Asakawa K, Kawakami K. Protocadherin-mediated cell repulsion controls the central topography and efferent projections of the abducens nucleus. Cell Reports, 24:1562-1572 (2018).4. Suberbielle E, Sanchez P, Kravitz A, Wang X, Ho K, Eilertson K, Devidze N, Kreitzer A, Mucke L. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β. Nature Neuroscience, 16: 613-621 (2013).5. Hughes A, Appel B. Microglia phagocytose myelin sheaths to modify developmental myelination. Nature Neuroscience, 23:1055-1066 (2020).6. Hill S, Mordes D, Cameron L, Neuberg D, Landini S, Eggan K, Livingston D. Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage. Proc Natl Acad Sci USA, 113:E7701–E7709 (2016).7. Mitra J, Guerrero E, Hegde P, Liachko N, Wang H, Vasquez V, Gao J, Pandey A, Taylor P, Kraemer B, Wu P, Boldogh I, Garruto R, Mitra S, Rao K, Hegde M. Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects. Proc Natl Acad Sci USA, 116:4696-4705 (2019).8. Konopka A, Whelan D, Jamali M, Perri E, Shahheydari H, Toth R, Parakh S, Robinson T, Cheong A, Mehta P, Vidal M, Ragagnin A, Khizhnyak I, Jagaraj C, Galper J, Grima N, Deva A, Shadfar S, Nicholson G, Yang S, Cutts S, Horejsi Z, Bell T, Walker A, Blair I, Atkin J. Impaired NHEJ repair in amyotrophic lateral sclerosis is associated with TDP-43 mutations. Molecular Neurodegeneration, 15:51 (2020).― 34 ―
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