Nah Jihoon, Yuan Junying, Jung Yong-Keun
Global Research Laboratory, School of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Korea.
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115-5730, USA.
Mol Cells. 2015 May;38(5):381-9. doi: 10.14348/molcells.2015.0034. Epub 2015 Apr 20.
Autophagy is a lysosome-dependent intracellular degradation process that allows recycling of cytoplasmic constituents into bioenergetic and biosynthetic materials for maintenance of homeostasis. Since the function of autophagy is particularly important in various stress conditions, perturbation of autophagy can lead to cellular dysfunction and diseases. Accumulation of abnormal protein aggregates, a common cause of neurodegenerative diseases, can be reduced through autophagic degradation. Recent studies have revealed defects in autophagy in most cases of neurodegenerative disorders. Moreover, deregulated excessive autophagy can also cause neurodegeneration. Thus, healthy activation of autophagy is essential for therapeutic approaches in neurodegenerative diseases and many autophagy-regulating compounds are under development for therapeutic purposes. This review describes the overall role of autophagy in neurodegeneration, focusing on various therapeutic strategies for modulating specific stages of autophagy and on the current status of drug development.
自噬是一种依赖溶酶体的细胞内降解过程，它能将细胞质成分循环利用为生物能量和生物合成材料，以维持体内稳态。由于自噬功能在各种应激条件下尤为重要，自噬的扰动会导致细胞功能障碍和疾病。异常蛋白质聚集体的积累是神经退行性疾病的常见原因，可通过自噬降解来减少。最近的研究表明，大多数神经退行性疾病病例中都存在自噬缺陷。此外，过度自噬失调也会导致神经退行性变。因此，自噬的健康激活对于神经退行性疾病的治疗方法至关重要，许多自噬调节化合物正在研发用于治疗目的。本综述描述了自噬在神经退行性变中的整体作用，重点关注调节自噬特定阶段的各种治疗策略以及药物开发的现状。
