Mechanistic insight into DNA damage and repair in ischemic stroke: exploiting the base excision repair pathway as a model of neuroprotection.
Stroke is a common cause of death and serious long-term adult disability. Oxidative DNA damage is a severe consequence of oxidative stress associated with ischemic stroke. The accumulation of DNA lesions, including oxidative base modifications and strand breaks, triggers cell death in neurons and other vulnerable cell populations in the ischemic brain. DNA repair systems, particularly base excision repair, are endogenous defense mechanisms that combat oxidative DNA damage. The capacity for DNA repair may affect the susceptibility of neurons to ischemic stress and influence the pathological outcome of stroke. This article reviews the accumulated understanding of molecular pathways by which oxidative DNA damage is triggered and repaired in ischemic cells, and the potential impact of these pathways on ischemic neuronal cell death/survival. Genetic or pharmacological strategies that target the signaling molecules in DNA repair responses are promising for potential clinically effective treatment. Further understanding of mechanisms for oxidative DNA damage and its repair processes may lead to new avenues for stroke management.
Li
Peiying
P
Anesthesiology Department of Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Hu
Xiaoming
X
Gan
Yu
Y
Gao
Yanqin
Y
Liang
Weimin
W
Chen
Jun
J
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology