Montreal Neurological Institute, McGill University, Montréal, QC, H3A 1A1, Canada; First Pavlov State Medical University of St. Petersburg, St. Petersburg, Russia; Petersburg Nuclear Physics Institute Named By B.P. Konstantinov of National Research Centre «Kurchatov Institute», Gatchina, Russia; Department of Human Genetics, McGill University, Montréal, QC, H3A 1A1, Canada.
Department of Neurology and Neurosurgery, McGill University, Montréal, QC, H3A 1A1, Canada; Montreal Neurological Institute, McGill University, Montréal, QC, H3A 1A1, Canada; Department of Human Genetics, McGill University, Montréal, QC, H3A 1A1, Canada.
Parkinsonism Relat Disord. 2020 Apr;73:60-71. doi: 10.1016/j.parkreldis.2019.11.015. Epub 2019 Nov 17.
In recent years, multiple lines of evidence from human genetic and molecular studies have highlighted the importance of the autophagy lysosomal pathway (ALP) in Parkinson's disease (PD). Genes such as GBA and LRRK2, which harbor some of the most common mutations associated with PD, have essential roles in the ALP. α-synuclein, encoded by the SNCA gene, is degraded mainly by the ALP, and mutations/multiplications in SNCA may lead to impairment of chaperone mediated autophagy or other ALP functions. Numerous other PD-related genes, such as PRKN, PINK1, TMEM175, SMPD1, CTSD, CTSB and many more, have also been reported to have important roles in the ALP. Understanding the relationship between ALP impairment and PD pathogenesis may be crucial for uncovering the mechanisms underlying PD, and for the development of long-awaited neuroprotective therapies. In this review, we will discuss the data linking the ALP to PD (other, atypical forms of Parkinsonism, will not be discussed in this review). We will focus on evidence from studies on specific genes and proteins, their roles in the ALP, and the potential mechanisms underlying the involvement of these genes in PD.
近年来，来自人类遗传和分子研究的多方面证据强调了自噬溶酶体途径 (ALP) 在帕金森病 (PD) 中的重要性。携带与 PD 相关的一些最常见突变的基因，如 GBA 和 LRRK2，在 ALP 中具有重要作用。α-突触核蛋白，由 SNCA 基因编码，主要通过 ALP 降解，而 SNCA 的突变/扩增可能导致伴侣介导的自噬或其他 ALP 功能受损。许多其他与 PD 相关的基因，如 PRKN、PINK1、TMEM175、SMPD1、CTSD、CTSB 等，也被报道在 ALP 中具有重要作用。了解 ALP 损伤与 PD 发病机制之间的关系可能对揭示 PD 的机制以及开发期待已久的神经保护疗法至关重要。在这篇综述中，我们将讨论将 ALP 与 PD 联系起来的研究数据（其他非典型帕金森病形式不在本次综述讨论范围内）。我们将重点讨论特定基因和蛋白质的研究证据，它们在 ALP 中的作用，以及这些基因参与 PD 的潜在机制。
