Dzamko Nicolas
Faculty of Medicine and Health and the Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
Biochem J. 2025 May 28;482(11):BCJ20253099. doi: 10.1042/BCJ20253099.
Leucine-rich repeat kinase 2 (LRRK2) has emerged as a promising therapeutic target for the treatment of neurodegenerative Parkinson's disease (PD). Data from a multitude of pre-clinical models are supportive of a potential role for LRRK2 therapies to ameliorate cellular dysfunctions found in PD, and small molecules to inhibit LRRK2 kinase activity, as well as antisense oligonucleotides to target the protein itself, are in clinical trials. Despite this, exactly how LRRK2 contributes to PD pathogenesis remains to be determined, and definitive biomarkers to track LRRK2 function are still required. Such biomarkers can be useful for monitoring the pharmacodynamic response of LRRK2 therapeutics and/or understanding the relationship between LRRK2 and the clinical progression of PD. Moreover, biomarkers that can identify increased LRRK2 levels or activity beyond just carriers of pathogenic LRRK2 mutations will be important for expanding LRRK2 therapeutics to other PD populations. This review summarizes recent findings regarding biomarkers of LRRK2.
富含亮氨酸重复激酶2（LRRK2）已成为治疗神经退行性帕金森病（PD）的一个有前景的治疗靶点。来自众多临床前模型的数据支持LRRK2疗法在改善PD中发现的细胞功能障碍方面的潜在作用，抑制LRRK2激酶活性的小分子以及靶向该蛋白本身的反义寡核苷酸正在进行临床试验。尽管如此，LRRK2究竟如何导致PD发病机制仍有待确定，并且仍然需要用于追踪LRRK2功能的确定性生物标志物。此类生物标志物可用于监测LRRK2疗法的药效学反应和/或理解LRRK2与PD临床进展之间的关系。此外，能够识别出除了致病性LRRK2突变携带者之外LRRK2水平或活性增加的生物标志物，对于将LRRK2疗法扩展到其他PD人群将具有重要意义。本综述总结了关于LRRK2生物标志物的最新发现。
