Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.

Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.
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DOI:
10.3390/ijms231911744
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发表时间:
2022-10-03
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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--
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帕金森氏症是影响老龄化人口的最常见的神经退行性疾病之一,其患病率在过去30年中翻了一番。由于该病的发病机制尚未完全阐明,目前的治疗方法无法有效预防神经退行性变。研究发现,富含亮氨酸的重复蛋白激酶2(LRRK2)的突变是家族性帕金森病(PD)最常见的原因。此外,LRRK2激酶活性异常(高)对特发性帕金森病也有影响。因此,本综述的目的是对与LRRK2相关的PD相关的现有信息进行分类和综合,并提出与LRRK2相关的可靶向治疗的因素。使用PubMed、Medline、Scope us、SAGE和Cochrane数据库进行了系统评价(2016年1月至2021年7月)。搜索关键词包括“帕金森病”,“机制”,“LRRK2”,以及不同组合的同义词。检索共产生了988篇摘要供初步审查,其中80篇符合纳入标准。在这里,我们强调最近在体内和体外研究揭示的分子机制。通过整合LRRK2相关PD领域的最新进展,研究人员可以进一步评估治疗应用的靶点。
Parkinson’s disease is one of the most common neurodegenerative diseases affecting the ageing population, with a prevalence that has doubled over the last 30 years. As the mechanism of the disease is not fully elucidated, the current treatments are unable to effectively prevent neurodegeneration. Studies have found that mutations in Leucine-rich-repeat-kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). Moreover, aberrant (higher) LRRK2 kinase activity has an influence in idiopathic PD as well. Hence, the aim of this review is to categorize and synthesize current information related to LRRK2-linked PD and present the factors associated with LRRK2 that can be targeted therapeutically. A systematic review was conducted using the databases PubMed, Medline, SCOPUS, SAGE, and Cochrane (January 2016 to July 2021). Search terms included “Parkinson’s disease”, “mechanism”, “LRRK2”, and synonyms in various combinations. The search yielded a total of 988 abstracts for initial review, 80 of which met the inclusion criteria. Here, we emphasize molecular mechanisms revealed in recent in vivo and in vitro studies. By consolidating the recent updates in the field of LRRK2-linked PD, researchers can further evaluate targets for therapeutic application.
DOI: 10.1038/s41531-017-0010-8
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帕金森氏病的遗传结构。
DOI: 10.1016/s1474-4422(19)30287-x
发表时间: 2020-02
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作者:
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通讯作者: Singleton AB