Laboratorio de Tráfico Intracelular y Señalización, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
J Neurosci Res. 2021 Jan;99(1):163-179. doi: 10.1002/jnr.24675. Epub 2020 Jul 7.
Parkinson's disease (PD) is a highly prevalent neurodegenerative condition. The disease involves the progressive degeneration of dopaminergic neurons located in the substantia nigra pars compacta. Among late-onset, familial forms of Parkinson are cases with mutations in the PARK17 locus encoding the vacuolar protein sorting 35 (Vps35), a subunit of the retromer complex. The retromer complex is composed of a heterotrimeric protein core (Vps26-Vps35-Vps29). The best-known role of retromer is the retrieval of cargoes from endosomes to the Golgi complex or the plasma membrane. However, recent literature indicates that retromer performs roles associated with lysosomal and mitochondrial functions and degradative pathways such as autophagy. A common point mutation affecting the retromer subunit Vps35 is D620N, which has been linked to the alterations in the aforementioned cellular processes as well as with neurodegeneration. Here, we review the main aspects of the malfunction of the retromer complex and its implications for PD pathology. Besides, we highlight several controversies still awaiting clarification.
帕金森病（PD）是一种高发的神经退行性疾病。该疾病涉及位于黑质致密部的多巴胺能神经元的进行性退化。在晚发性、家族性帕金森病中，有一些病例是 PARK17 基因座编码空泡蛋白分选 35（Vps35）的突变，Vps35 是逆行转运复合体的一个亚基。逆行转运复合体由一个异三聚体蛋白核心（Vps26-Vps35-Vps29）组成。逆行转运复合体最著名的作用是从内体中回收货物到高尔基体或质膜。然而，最近的文献表明，逆行转运复合体还具有与溶酶体和线粒体功能以及自噬等降解途径相关的作用。影响逆行转运复合体亚基 Vps35 的常见点突变是 D620N，它与上述细胞过程的改变以及神经退行性变有关。在这里，我们回顾了逆行转运复合体功能障碍的主要方面及其对 PD 病理学的影响。此外，我们还强调了一些仍有待澄清的争议。
