Manzoni Claudia, Lewis Patrick A
School of Pharmacy, University of Reading, Whiteknights, Reading, UK.
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
Adv Neurobiol. 2017;14:89-105. doi: 10.1007/978-3-319-49969-7_5.
Leucine-rich repeat kinase 2 (LRRK2) has been implicated in a wide range of cellular processes, including the catabolic pathways collectively described as autophagy. In this chapter, the evidence linking LRRK2 to autophagy will be examined, along with how regulation of autophagy and lysosomal pathways may provide a nexus between the physiological function of this protein and the different diseases with which it has been associated. Data from cellular and animal models for LRRK2 function and dysfunction support a role in the regulation and control of autophagic pathways in the cell, although the extant results do not provide a clear indication as to whether LRRK2 is a positive or negative regulator of these pathways, and there are conflicting data as to the impact of mutations in LRRK2 causative for Parkinson's disease. Given that LRRK2 is a priority drug target for Parkinson's, the evidence suggesting that knockout or inhibition of LRRK2 can result in deregulation of autophagy may have important implications and is discussed in the context of our wider understanding of LRRK2.
富含亮氨酸重复激酶2（LRRK2）参与了广泛的细胞过程，包括统称为自噬的分解代谢途径。在本章中，将研究将LRRK2与自噬联系起来的证据，以及自噬和溶酶体途径的调节如何在该蛋白的生理功能与其相关的不同疾病之间提供联系。来自LRRK2功能和功能障碍的细胞及动物模型的数据支持其在细胞自噬途径的调节和控制中发挥作用，尽管现有结果并未明确表明LRRK2是这些途径的正调节因子还是负调节因子，并且关于导致帕金森病的LRRK2突变的影响存在相互矛盾的数据。鉴于LRRK2是帕金森病的优先药物靶点，表明敲除或抑制LRRK2会导致自噬失调的证据可能具有重要意义，并将在我们对LRRK2的更广泛理解的背景下进行讨论。
