Geriatric Research Education and Clinical Center, VA Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, California, USA.
Mol Neurodegener. 2009 Apr 6;4:16. doi: 10.1186/1750-1326-4-16.
Autophagy is the major pathway involved in the degradation of proteins and organelles, cellular remodeling, and survival during nutrient starvation. Autophagosomal dysfunction has been implicated in an increasing number of diseases from cancer to bacterial and viral infections and more recently in neurodegeneration. While a decrease in autophagic activity appears to interfere with protein degradation and possibly organelle turnover, increased autophagy has been shown to facilitate the clearance of aggregation-prone proteins and promote neuronal survival in a number of disease models. On the other hand, too much autophagic activity can be detrimental as well and lead to cell death, suggesting the regulation of autophagy has an important role in cell fate decisions. An increasing number of model systems are now available to study the role of autophagy in the central nervous system and how it might be exploited to treat disease. We will review here the current knowledge of autophagy in the central nervous system and provide an overview of the various models that have been used to study acute and chronic neurodegeneration.
自噬是参与蛋白质和细胞器降解、细胞重塑以及营养饥饿期间存活的主要途径。越来越多的疾病，从癌症到细菌和病毒感染，最近甚至在神经退行性疾病中，都与自噬体功能障碍有关。虽然自噬活性的降低似乎会干扰蛋白质降解，可能还会影响细胞器的更新，但已经表明增加自噬可以促进易于聚集的蛋白质的清除，并在许多疾病模型中促进神经元存活。另一方面，过多的自噬活性也可能有害并导致细胞死亡，这表明自噬的调节在细胞命运决定中起着重要作用。现在有越来越多的模型系统可用于研究自噬在中枢神经系统中的作用以及如何利用它来治疗疾病。我们将在这里回顾中枢神经系统中自噬的现有知识，并概述用于研究急性和慢性神经退行性变的各种模型。
