Department of Pharmacology, Second Military Medical University, Shanghai, China.
CNS Neurosci Ther. 2012 Nov;18(11):879-86. doi: 10.1111/cns.12005. Epub 2012 Sep 24.
Cerebral ischemia is a severe outcome that could cause cognitive and motor dysfunction, neurodegenerative diseases and even acute death. Although the existence of autophagy in cerebral ischemia is undisputable, the consensus has not yet been reached regarding the exact functions and influence of autophagy in cerebral ischemia. Whether the activation of autophagy is beneficial or harmful in cerebral ischemia injury largely depends on the balance between the burden of intracellular substrate targeted for autophagy and the capacity of the cellular autophagic machinery. Furthermore, the mechanisms underlying the autophagy in cerebral ischemia are far from clear yet. This brief review focuses on not only the current understanding of biological effects of autophagy, but also the therapeutic potentials of autophagy in ischemic stroke. There are disputes over the exact role of autophagy in cerebral ischemia. Application of chemical autophagy inhibitor (e.g., 3-methyladenine) or inducer (e.g., rapamycin) in vitro and in vivo was reported to protect or harm neuronal cell. Knockdown of autophagic protein, such as Beclin 1, was also reported to modulate the cerebral ischemia-induced injury. Moreover, autophagy inhibitor abolished the neuroprotection of ischemic preconditioning, implying a neuroprotective effect of autophagy. To clarify these issues on autophagy in cerebral ischemia, future investigations are warranted.
脑缺血是一种严重的后果，可导致认知和运动功能障碍、神经退行性疾病甚至急性死亡。尽管脑缺血中自噬的存在是无可争议的，但自噬在脑缺血中的确切功能和影响尚未达成共识。自噬在脑缺血损伤中是有益还是有害，在很大程度上取决于细胞内自噬靶向底物的负担与细胞自噬机制的能力之间的平衡。此外，脑缺血中自噬的机制还远未清楚。这篇简短的综述不仅关注自噬的生物学效应的当前理解，还关注自噬在缺血性中风中的治疗潜力。自噬在脑缺血中的确切作用存在争议。有报道称，在体外和体内应用化学自噬抑制剂（如 3-甲基腺嘌呤）或诱导剂（如雷帕霉素）可保护或损害神经元细胞。自噬蛋白（如 Beclin 1）的敲低也被报道可调节脑缺血诱导的损伤。此外，自噬抑制剂消除了缺血预处理的神经保护作用，这意味着自噬具有神经保护作用。为了澄清脑缺血中自噬的这些问题，需要进一步的研究。
