Katyal Sachin, McKinnon Peter J
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Mech Ageing Dev. 2008 Jul-Aug;129(7-8):483-91. doi: 10.1016/j.mad.2008.03.008. Epub 2008 Mar 25.
Defective responses to DNA single- or double-strand breaks can result in neurological disease, underscoring the critical importance of DNA repair for neural homeostasis. Human DNA repair-deficient syndromes are generally congenital, in which brain pathology reflects the consequences of developmentally incurred DNA damage. Although, it is unclear to what degree DNA strand-break repair defects in mature neural cells contributes to disease pathology. However, DNA single-strand breaks are a relatively common lesion which if not repaired can impact cells via interference with transcription. Thus, this lesion, and probably to a lesser extent DNA double-strand breaks, may be particularly relevant to aging in the neural cell population. In this review we will examine the consequences of defective DNA strand-break repair towards homeostasis in the brain. Further, we also consider the utility of mouse models as reagents to understand the connection between DNA strand breaks and aging in the brain.
对DNA单链或双链断裂的缺陷反应可导致神经疾病，这突出了DNA修复对神经内环境稳定的至关重要性。人类DNA修复缺陷综合征通常是先天性的，其中脑病理学反映了发育过程中发生的DNA损伤的后果。然而，尚不清楚成熟神经细胞中的DNA链断裂修复缺陷在多大程度上导致疾病病理。不过，DNA单链断裂是一种相对常见的损伤，如果不修复，可能会通过干扰转录影响细胞。因此，这种损伤，可能在较小程度上还有DNA双链断裂，可能与神经细胞群体的衰老特别相关。在这篇综述中，我们将研究有缺陷的DNA链断裂修复对脑内环境稳定的影响。此外，我们还将探讨小鼠模型作为试剂在理解DNA链断裂与脑衰老之间联系方面的作用。
