Department of Neurology, Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan.
Int J Mol Sci. 2024 Jul 19;25(14):7906. doi: 10.3390/ijms25147906.
Neurons in the brain are continuously exposed to various sources of DNA damage. Although the mechanisms of DNA damage repair in mitotic cells have been extensively characterized, the repair pathways in post-mitotic neurons are still largely elusive. Moreover, inaccurate repair can result in deleterious mutations, including deletions, insertions, and chromosomal translocations, ultimately compromising genomic stability. Since neurons are terminally differentiated cells, they cannot employ homologous recombination (HR) for double-strand break (DSB) repair, suggesting the existence of neuron-specific repair mechanisms. Our research has centered on the microtubule-associated protein tau (MAPT), a crucial pathological protein implicated in neurodegenerative diseases, and its interplay with neurons' DNA damage response (DDR). This review aims to provide an updated synthesis of the current understanding of the complex interplay between DDR and cytoskeletal proteins in neurons, with a particular focus on the role of tau in neurodegenerative disorders.
大脑中的神经元持续暴露于各种 DNA 损伤源中。尽管有丝分裂细胞中 DNA 损伤修复的机制已被广泛研究，但在后丝裂神经元中的修复途径仍在很大程度上难以捉摸。此外，不准确的修复可能导致有害的突变，包括缺失、插入和染色体易位，最终损害基因组稳定性。由于神经元是终末分化的细胞，它们不能利用同源重组（HR）进行双链断裂（DSB）修复，这表明存在神经元特异性的修复机制。我们的研究集中在微管相关蛋白 tau（MAPT）上，它是一种与神经退行性疾病有关的关键病理蛋白，以及它与神经元的 DNA 损伤反应（DDR）之间的相互作用。这篇综述旨在提供对 DDR 与神经元中细胞骨架蛋白之间复杂相互作用的最新综合理解，特别关注 tau 在神经退行性疾病中的作用。
