Department of Neurology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Department of Research for Parkinson's Disease, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Biomolecules. 2023 Jan 15;13(1):178. doi: 10.3390/biom13010178.
Leucine rich-repeat kinase 2 () is the most well-known etiologic gene for familial Parkinson's disease (PD). Its gene product is a large kinase with multiple functional domains that phosphorylates a subset of Rab small GTPases. However, studies of autopsy cases with LRRK2 mutations indicate a varied pathology, and the molecular functions of LRRK2 and its relationship to PD pathogenesis are largely unknown. Recently, non-autonomous neurodegeneration associated with glial cell dysfunction has attracted attention as a possible mechanism of dopaminergic neurodegeneration. Molecular studies of LRRK2 in astrocytes and microglia have also suggested that LRRK2 is involved in the regulation of lysosomal and other organelle dynamics and inflammation. In this review, we describe the proposed functions of LRRK2 in glial cells and discuss its involvement in the pathomechanisms of PD.
富含亮氨酸重复激酶 2（LRRK2）是最著名的家族性帕金森病（PD）的病因基因。其基因产物是一种具有多个功能结构域的大型激酶，可磷酸化一组 Rab 小分子 GTP 酶。然而，对具有 LRRK2 突变的尸检病例的研究表明存在多种病理学，LRRK2 的分子功能及其与 PD 发病机制的关系在很大程度上尚不清楚。最近，与神经胶质细胞功能障碍相关的非自主神经退行性变作为多巴胺能神经退行性变的可能机制引起了关注。对星形胶质细胞和小胶质细胞中 LRRK2 的分子研究也表明，LRRK2 参与调节溶酶体和其他细胞器的动态以及炎症。在这篇综述中，我们描述了 LRRK2 在神经胶质细胞中的拟议功能，并讨论了其在 PD 发病机制中的作用。
