Neuronal macroautophagy: From development to degeneration
Neuronal macroautophagy: From development to degeneration
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DOI：
10.1016/j.mam.2006.08.009
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发表时间：
2006-10-01
影响因子：
10.6
通讯作者：
Nixon, Ralph A.
中科院分区：
文献类型：
--
作者：
Boland, Barry;Nixon, Ralph A.
大自噬是一种溶酶体途径，负责细胞器和长寿命蛋白的周转，主要被认为是神经元中的诱导过程，在应激和损伤状态下被动员。然而，新的研究表明，宏自噬在健康的神经元中也是组成性活跃的，对细胞存活至关重要。与外周细胞不同，大脑中的神经元受到保护，不受大规模自噬诱导的影响，因为它们可以最佳地使用几种不同的能量来源，从神经胶质细胞获得额外的营养素和神经营养素支持，并受益于下丘脑对外周营养供应的调节。由于其异常的效率，健康神经元中的组成性自噬在不存在容易检测到的自噬空泡中间体的情况下进行。这些中间产物可以迅速积累。然而，当自噬过程的后期步骤被阻断时。自噬空泡还在几种主要神经退行性疾病（包括阿尔茨海默病和帕金森病）的受影响神经元中异常积累，其中它们与疾病发病机制的各个方面（包括神经元细胞死亡）相关。在这些神经系统疾病和其他疾病中自噬空泡的建立可能反映了自噬诱导的增强，自噬途径中后期消化步骤的损伤，或两者兼而有之。确定AV积累的基础对于理解自噬在给定病理状态下的致病意义和设计基于调节自噬的可能疗法至关重要。在这篇综述中，我们讨论了自噬调节在大脑中的特殊功能，其在神经发育和可塑性中的可疑作用，以及了解功能失调的自噬如何导致神经退行性疾病的最新进展。(c)2006爱思唯尔有限公司保留所有权利。
Macroautophagy, a lysosomal pathway responsible for the turnover of organelles and long-lived proteins, has been regarded mainly as an inducible process in neurons, which is mobilized in states of stress and injury. New studies show, however, that macroautophagy is also constitutively active in healthy neurons and is vital to cell survival. Neurons in the brain, unlike cells in the periphery, are protected from large-scale autophagy induction because they can use several different energy sources optimally, receive additional nutrients and neurotrophin support from glial cells, and benefit from hypothalamic regulation of peripheral nutrient supplies. Due to its exceptional efficiency, constitutive autophagy in healthy neurons proceeds in the absence of easily detectable autophagic vacuole intermediates. These intermediates can accumulate rapidly.. however, when late steps in the autophagic process are blocked. Autophagic vacuoles also accumulate abnormally in affected neurons of several major neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, where they have been linked to various aspects of disease pathogenesis including neuronal cell death. The build-up of autophagic vacuoles in these neurological disorders and others may reflect either heightened autophagy induction, impairment in later digestive steps in the autophagy pathway, or both. Determining the basis for AV accumulation is critical for understanding the pathogenic significance of autophagy in a given pathologic state and for designing possible therapies based on modulating autophagy. In this review, we discuss the special features of autophagy regulation in the brain, its suspected roles in neurodevelopment and plasticity, and recent progress toward understanding how dysfunctional autophagy contributes to neurodegenerative disease. (c) 2006 Elsevier Ltd. All rights reserved.