Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, U.K.
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, U.K.
Clin Sci (Lond). 2022 Jul 15;136(13):1071-1079. doi: 10.1042/CS20220067.
Parkinson's disease (PD) is conventionally described as an α-synuclein aggregation disorder, defined by Lewy bodies and neurites, and mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common autosomal dominant cause of PD. However, LRRK2 mutations may be associated with diverse pathologies in patients with Parkinson's syndrome including tau pathology resembling progressive supranuclear palsy (PSP). The recent discovery that variation at the LRRK2 locus is associated with the progression of PSP highlights the potential importance of LRRK2 in tauopathies. Here, we review the emerging evidence and discuss the potential impact of LRRK2 dysfunction on tau aggregation, lysosomal function, and endocytosis and exocytosis.
帕金森病（PD）通常被描述为一种α-突触核蛋白聚集障碍，其特征是路易体和神经突，富亮氨酸重复激酶 2（LRRK2）突变是 PD 最常见的常染色体显性遗传原因。然而，LRRK2 突变可能与帕金森综合征患者的多种病理学有关，包括类似于进行性核上性麻痹（PSP）的tau 病理学。最近发现，LRRK2 基因座的变异与 PSP 的进展有关，这突显了 LRRK2 在 tau 病中的潜在重要性。在这里，我们回顾了新出现的证据，并讨论了 LRRK2 功能障碍对 tau 聚集、溶酶体功能以及内吞作用和胞吐作用的潜在影响。
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