Sanchiz-Calvo María, Bentea Eduard, Baekelandt Veerle
Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
Curr Opin Neurobiol. 2022 Feb;72:55-62. doi: 10.1016/j.conb.2021.09.004. Epub 2021 Oct 7.
Genes associated with endolysosomal function have been recently associated with familial Parkinson's disease and described as risk factors for sporadic cases. This indicates that deficits in this pathway predispose to parkinsonism. To better understand the role of these genes in disease development, rodent models have been created by targeting genes playing a role in endolysosomal function, such as LRRK2, DNAJC6, SYNJ1, VPS35, GBA1, ATP13A2 and TMEM175. Here, we review the latest findings describing parkinsonian features in these animal models secondary to endolysosomal dysfunction. Also, we provide suggestions for further development and application of these animal models to better understand the contribution of endolysosomal dysfunction in Parkinson's disease and provide novel models for testing therapeutic approaches.
与内溶酶体功能相关的基因最近已与家族性帕金森病相关联，并被描述为散发性病例的风险因素。这表明该通路的缺陷易导致帕金森综合征。为了更好地理解这些基因在疾病发展中的作用，通过靶向在内溶酶体功能中起作用的基因，如LRRK2、DNAJC6、SYNJ1、VPS35、GBA1、ATP13A2和TMEM175，创建了啮齿动物模型。在此，我们综述了描述这些动物模型中继发于内溶酶体功能障碍的帕金森病特征的最新发现。此外，我们为这些动物模型的进一步开发和应用提供建议，以更好地理解内溶酶体功能障碍在帕金森病中的作用，并为测试治疗方法提供新的模型。
