当前位置: X-MOL 学术Front. Mol. Neurosci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A Critical LRRK at the Synapse? The Neurobiological Function and Pathophysiological Dysfunction of LRRK2
Frontiers in Molecular Neuroscience ( IF 3.5 ) Pub Date : 2020-07-22 , DOI: 10.3389/fnmol.2020.00153
Naila Kuhlmann , Austen J. Milnerwood

Since the discovery of LRRK2 mutations causal to Parkinson’s disease (PD) in the early 2000s, the LRRK2 protein has been implicated in a plethora of cellular processes in which pathogenesis could occur, yet its physiological function remains elusive. The development of genetic models of LRRK2 PD has helped identify the etiological and pathophysiological underpinnings of the disease, and may identify early points of intervention. An important role for LRRK2 in synaptic function has emerged in recent years, which links LRRK2 to other genetic forms of PD, most notably those caused by mutations in the synaptic protein α-synuclein. This point of convergence may provide useful clues as to what drives dysfunction in the basal ganglia circuitry and eventual death of substantia nigra (SN) neurons. Here, we discuss the evolution and current state of the literature placing LRRK2 at the synapse, through the lens of knock-out, overexpression, and knock-in animal models. We hope that a deeper understanding of LRRK2 neurobiology, at the synapse and beyond, will aid the eventual development of neuroprotective interventions for PD, and the advancement of useful treatments in the interim.



中文翻译:

突触中的关键LRRK?LRRK2的神经生物学功能和病理生理功能障碍

自发现以来 LRRK2在2000年代初期,由于帕金森氏病(PD)的突变,LRR​​K2蛋白已经参与了许多可能发生发病的细胞过程,但其生理功能仍然难以捉摸。LRRK2 PD遗传模型的开发已帮助确定该病的病因和病理生理基础,并可能确定早期干预点。近年来,LRRK2在突触功能中发挥了重要作用,这将LRRK2与PD的其他遗传形式联系起来,最显着的是那些由突触蛋白α-突触核蛋白突变引起的。这个收敛点可能为有关什么驱动基底神经节功能障碍以及黑质(SN)神经元最终死亡提供有用的线索。这里,我们通过敲除,过度表达和敲入动物模型的角度讨论了将LRRK2置于突触的文献的演变和当前状态。我们希望,对突触及更远处的LRRK2神经生物学的更深入了解,将有助于最终开发出针对PD的神经保护性干预措施,并在此期间促进有用治疗的发展。

更新日期:2020-08-27
down
wechat
bug