富含亮氨酸重复激酶2的帕金森病生物标志物。

IF 4.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nicolas Dzamko
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引用次数: 0

摘要

富亮氨酸重复激酶2 (LRRK2)已成为治疗神经退行性帕金森病(PD)的一个有希望的治疗靶点。来自大量临床前模型的数据支持LRRK2治疗在改善PD中发现的细胞功能障碍方面的潜在作用,并且抑制LRRK2激酶活性的小分子以及针对蛋白质本身的反义寡核苷酸正在临床试验中。尽管如此,LRRK2在帕金森病发病机制中的确切作用仍有待确定,并且仍然需要明确的生物标志物来追踪LRRK2的功能。这些生物标志物可用于监测LRRK2治疗药物的药效学反应和/或了解LRRK2与PD临床进展之间的关系。此外,能够识别致病LRRK2突变携带者以外LRRK2水平或活性增加的生物标志物对于将LRRK2治疗扩展到其他PD人群将是重要的。本文综述了近年来有关LRRK2生物标志物的研究进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Leucine-rich repeat kinase 2 biomarkers for Parkinson's disease.

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.

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来源期刊
Biochemical Journal
Biochemical Journal 生物-生化与分子生物学
CiteScore
8.00
自引率
0.00%
发文量
255
审稿时长
1 months
期刊介绍: Exploring the molecular mechanisms that underpin key biological processes, the Biochemical Journal is a leading bioscience journal publishing high-impact scientific research papers and reviews on the latest advances and new mechanistic concepts in the fields of biochemistry, cellular biosciences and molecular biology. The Journal and its Editorial Board are committed to publishing work that provides a significant advance to current understanding or mechanistic insights; studies that go beyond observational work using in vitro and/or in vivo approaches are welcomed. Painless publishing: All papers undergo a rigorous peer review process; however, the Editorial Board is committed to ensuring that, if revisions are recommended, extra experiments not necessary to the paper will not be asked for. Areas covered in the journal include: Cell biology Chemical biology Energy processes Gene expression and regulation Mechanisms of disease Metabolism Molecular structure and function Plant biology Signalling
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