Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland.
Int J Mol Sci. 2023 Sep 7;24(18):13793. doi: 10.3390/ijms241813793.
Autophagy is a self-defense and self-degrading intracellular system involved in the recycling and elimination of the payload of cytoplasmic redundant components, aggregated or misfolded proteins and intracellular pathogens to maintain cell homeostasis and physiological function. Autophagy is activated in response to metabolic stress or starvation to maintain homeostasis in cells by updating organelles and dysfunctional proteins. In neurodegenerative diseases, such as cerebral ischemia, autophagy is disturbed, e.g., as a result of the pathological accumulation of proteins associated with Alzheimer's disease and their structural changes. Postischemic brain neurodegeneration, such as Alzheimer's disease, is characterized by the accumulation of amyloid and tau protein. After cerebral ischemia, autophagy was found to be activated in neuronal, glial and vascular cells. Some studies have shown the protective properties of autophagy in postischemic brain, while other studies have shown completely opposite properties. Thus, autophagy is now presented as a double-edged sword with possible therapeutic potential in brain ischemia. The exact role and regulatory pathways of autophagy that are involved in cerebral ischemia have not been conclusively elucidated. This review aims to provide a comprehensive look at the advances in the study of autophagy behavior in neuronal, glial and vascular cells for ischemic brain injury. In addition, the importance of autophagy in neurodegeneration after cerebral ischemia has been highlighted. The review also presents the possibility of modulating the autophagy machinery through various compounds on the development of neurodegeneration after cerebral ischemia.
自噬是一种参与细胞质冗余成分、聚集或错误折叠蛋白质和细胞内病原体的回收和消除的自我防御和自我降解的细胞内系统，以维持细胞内的平衡和生理功能。自噬在代谢应激或饥饿时被激活，通过更新细胞器和功能失调的蛋白质来维持细胞内的平衡。在神经退行性疾病中，如脑缺血，自噬被扰乱，例如由于与阿尔茨海默病相关的蛋白质的病理性积累及其结构变化。脑缺血后神经退行性变，如阿尔茨海默病，其特征是淀粉样蛋白和tau 蛋白的积累。在脑缺血后，自噬在神经元、神经胶质细胞和血管细胞中被发现被激活。一些研究表明自噬在脑缺血后的保护特性，而其他研究则表明完全相反的特性。因此，自噬现在被认为是一把双刃剑，在脑缺血中具有潜在的治疗作用。自噬在脑缺血中的确切作用和调节途径尚未得到明确阐明。本综述旨在全面了解神经元、神经胶质细胞和血管细胞自噬行为在脑缺血损伤中的研究进展。此外，还强调了自噬在脑缺血后神经退行性变中的重要性。该综述还提出了通过各种化合物调节自噬机制在脑缺血后神经退行性变发展中的可能性。
