McCray Brett A, Taylor J Paul
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Neurosignals. 2008;16(1):75-84. doi: 10.1159/000109761. Epub 2007 Dec 5.
Most age-related neurodegenerative diseases are characterized by accumulation of aberrant protein aggregates in affected brain regions. In many cases, these proteinaceous deposits are composed of ubiquitin conjugates, suggesting a failure in the clearance of proteins targeted for degradation. The 2 principal routes of intracellular protein catabolism are the ubiquitin proteasome system and the autophagy-lysosome system (autophagy). Both of these degradation pathways have been implicated as playing important roles in the pathogenesis of neurodegenerative disease. Here we describe autophagy and review the evidence suggesting that impairment of autophagy contributes to the initiation or progression of age-related neurodegeneration. We also review recent evidence indicating that autophagy may be exploited to remove toxic protein species, suggesting novel strategies for therapeutic intervention for a class of diseases for which no effective treatments presently exist.
大多数与年龄相关的神经退行性疾病的特征是在受影响的脑区中异常蛋白质聚集体的积累。在许多情况下，这些蛋白质沉积物由泛素缀合物组成，这表明针对降解的蛋白质清除存在缺陷。细胞内蛋白质分解代谢的2条主要途径是泛素蛋白酶体系统和自噬-溶酶体系统（自噬）。这两种降解途径都被认为在神经退行性疾病的发病机制中起重要作用。在这里，我们描述自噬并综述证据，这些证据表明自噬受损有助于与年龄相关的神经退行性变的起始或进展。我们还综述了最近的证据，表明自噬可用于清除有毒蛋白质种类，这为一类目前尚无有效治疗方法的疾病提出了新的治疗干预策略。
