Gómez Olga, Perini-Villanueva Giuliana, Yuste Andrea, Rodríguez-Navarro José Antonio, Poch Enric, Bejarano Eloy
School of Health Sciences and Veterinary School, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, Spain.
Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States.
Front Cell Dev Biol. 2021 Dec 23;9:790479. doi: 10.3389/fcell.2021.790479. eCollection 2021.
Autophagy is a fine-tuned proteolytic pathway that moves dysfunctional/aged cellular components into the lysosomal compartment for degradation. Over the last 3 decades, global research has provided evidence for the protective role of autophagy in different brain cell components. Autophagic capacities decline with age, which contributes to the accumulation of obsolete/damaged organelles and proteins and, ultimately, leads to cellular aging in brain tissues. It is thus well-accepted that autophagy plays an essential role in brain homeostasis, and malfunction of this catabolic system is associated with major neurodegenerative disorders. Autophagy function can be modulated by different types of stress, including glycative stress. Glycative stress is defined as a cellular status with abnormal and accelerated accumulation of advanced glycation end products (AGEs). It occurs in hyperglycemic states, both through the consumption of high-sugar diets or under metabolic conditions such as diabetes. In recent years, glycative stress has gained attention for its adverse impact on brain pathology. This is because glycative stress stimulates insoluble, proteinaceous aggregation that is linked to the malfunction of different neuropathological proteins. Despite the emergence of new literature suggesting that autophagy plays a major role in fighting glycation-derived damage by removing cytosolic AGEs, excessive glycative stress might also negatively impact autophagic function. In this mini-review, we provide insight on the status of present knowledge regarding the role of autophagy in brain physiology and pathophysiology, with an emphasis on the cytoprotective role of autophagic function to ameliorate the adverse effects of glycation-derived damage in neurons, glia, and neuron-glia interactions.
自噬是一种精细调节的蛋白水解途径，它将功能失调/老化的细胞成分转运到溶酶体区室进行降解。在过去三十年中，全球研究已为自噬在不同脑细胞成分中的保护作用提供了证据。自噬能力会随着年龄增长而下降，这会导致陈旧/受损细胞器和蛋白质的积累，并最终导致脑组织细胞衰老。因此，人们普遍认为自噬在脑稳态中起着至关重要的作用，而这种分解代谢系统的功能失调与主要的神经退行性疾病有关。自噬功能可受到不同类型应激的调节，包括糖基化应激。糖基化应激被定义为晚期糖基化终产物（AGEs）异常且加速积累的细胞状态。它发生在高血糖状态下，既可以通过高糖饮食的摄入，也可以在诸如糖尿病等代谢条件下发生。近年来，糖基化应激因其对脑病理学的不利影响而受到关注。这是因为糖基化应激会刺激与不同神经病理蛋白功能障碍相关的不溶性蛋白质聚集。尽管有新文献表明自噬通过清除胞质AGEs在对抗糖基化衍生损伤中起主要作用，但过度的糖基化应激也可能对自噬功能产生负面影响。在本综述中，我们深入探讨了关于自噬在脑生理和病理生理中的作用的现有知识状况，重点是自噬功能在减轻神经元、神经胶质细胞以及神经元 - 神经胶质细胞相互作用中糖基化衍生损伤的不良影响方面的细胞保护作用。
