CIBIO, Università degli Studi di Trento, Italy & Dulbecco Telethon Institute, Trento, Italy.
J Neurochem. 2021 Apr;157(2):297-311. doi: 10.1111/jnc.15240. Epub 2021 Feb 5.
Parkinson's disease is a common neurodegenerative disorder and is clinically characterized by bradykinesia, rigidity, and resting tremor. Missense mutations in the leucine-rich repeat protein kinase-2 gene (LRRK2) are a recognized cause of inherited Parkinson's disease. The physiological and pathological impact of LRRK2 is still obscure, but accumulating evidence indicates that LRRK2 orchestrates diverse aspects of membrane trafficking, such as membrane fusion and vesicle formation and transport along actin and tubulin tracks. In the present review, we focus on the special relation between LRRK2 and synaptic vesicles. LRRK2 binds and phosphorylates key actors within the synaptic vesicle cycle. Accordingly, alterations in dopamine and glutamate transmission have been described upon LRRK2 manipulations. However, the different modeling strategies and phenotypes observed require a critical approach to decipher the outcome of LRRK2 at the pre-synaptic site.
帕金森病是一种常见的神经退行性疾病，临床上以运动迟缓、肌肉强直和静止性震颤为特征。富含亮氨酸重复序列蛋白激酶 2 基因（LRRK2）的错义突变是遗传性帕金森病的公认病因。LRRK2 的生理和病理影响仍不清楚，但越来越多的证据表明，LRRK2 协调膜运输的多个方面，如膜融合以及沿着肌动蛋白和微管轨道形成和运输囊泡。在本综述中，我们重点关注 LRRK2 与突触囊泡之间的特殊关系。LRRK2 结合并磷酸化突触囊泡循环中的关键因子。因此，LRRK2 的操作会引起多巴胺和谷氨酸传递的改变。然而，观察到的不同建模策略和表型需要批判性地解析 LRRK2 在突触前部位的作用。
