Weill Cornell Medical College, Biochemistry Department, 1300 York Ave, New York, NY 10021, USA.
Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S154-7. doi: 10.1016/S1353-8020(13)70037-3.
Genetic studies over the past 15 years have revolutionized our understanding towards the etiology of Parkinson's disease (PD). These studies have discovered many disease-linked genetic loci (PARK 1 to 18), which are now being interrogated for cellular pathways contributing to PD. Various pathogenic pathways were proposed but validation of each pathway awaits rigorous experimental testing. Here we review recent progress in understanding the influence of disease risk genes on cellular functions, specifically, autophagy pathways. Autophagy is a cell self-eating, lysosomal degradation system that plays an important role in cell homeostasis and survival. Neurons are post-mitotic cells and particularly vulnerable to the impairment of autophagic degradation due to their inability to redistribute damaged proteins and organelles to daughter cells. Emerging evidence has implicated dysfunctional autophagy in a growing number of neurodegenerative diseases including PD. We will also discuss the prospect of intervening autophagy pathways as a potential strategy to treat PD.
在过去的 15 年中，遗传研究彻底改变了我们对帕金森病 (PD) 病因的理解。这些研究发现了许多与疾病相关的遗传基因座（PARK1 至 18），目前正在研究这些基因座在导致 PD 方面的细胞途径。已经提出了各种致病途径，但每个途径的验证都需要严格的实验测试。在这里，我们回顾了理解疾病风险基因对细胞功能，特别是自噬途径影响的最新进展。自噬是一种细胞自我吞噬、溶酶体降解系统，在细胞内稳态和存活中发挥着重要作用。神经元是有丝分裂后的细胞，由于其无法将受损的蛋白质和细胞器重新分配到子细胞中，因此特别容易受到自噬降解功能障碍的影响。越来越多的证据表明，自噬功能障碍与包括 PD 在内的许多神经退行性疾病有关。我们还将讨论干预自噬途径作为治疗 PD 的一种潜在策略的前景。
