LRRKing up the right trees? On figuring out the effects of mutant LRRK2 and other Parkinson's disease-related genes.
LRRKing up the right trees? On figuring out the effects of mutant LRRK2 and other Parkinson's disease-related genes.
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LRRK 爬上正确的树吗？
DOI：
10.1016/j.baga.2013.04.002
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Steiner,Heinz
中科院分区：
文献类型：
--
作者：
Steiner,Heinz
特定基因与帕金森病（PD）之间的关联已经被发现了10多年，现在人们认为这些PD（风险）基因的突变可能与其他因素相互作用，是PD的主要原因[1-4]。这些PD危险基因包括α -突触核蛋白（SNCA）、LRRK2、Parkin、PINK1等。然而，经过十年的深入研究，人们仍然不清楚这些基因中的大多数突变是如何导致PD病理的。这可能是由于许多原因，包括其中一些基因似乎编码具有多种功能的复杂分子；突变可能导致毒性的功能获得和/或功能丧失缺陷；突变分子可能需要相互作用或其他影响才能有效；或者这些分子或它们的产物可能需要从其他大脑结构迁移，甚至从外围迁移到它们应该杀死的多巴胺神经元。这些因素都使PD危险基因的作用机制分析复杂化。
It has been 10 years and more since associations between specific genes and Parkinson’s disease (PD) were discovered, and it is now assumed that mutations in such PD (risk) genes, probably in interaction with other factors, are a major cause for PD [1–4]. These PD risk genes include alpha-synuclein (SNCA), LRRK2, Parkin, PINK1 and others. Yet after a decade of intense research it is still unclear how most mutations in these genes contribute to the PD pathology. This is likely due to a number of reasons, including that some of these genes seem to encode complex molecules with multiple functions; that mutations may lead to toxic gain-of-function and/or loss-of-function defects; that mutated molecules may need to interact with one another or other influences to be effective; or that some of these molecules or their products may need to migrate from other brain structures or even from the periphery to the dopamine neurons that they are supposed to kill. These factors all complicate the analysis of the mechanisms of action of PD risk genes.