Devine Michael J, Lewis Patrick A
Department of Clinical Neuroscience, Imperial College London, UK.
FEBS J. 2008 Dec;275(23):5748-57. doi: 10.1111/j.1742-4658.2008.06707.x.
The last decade has seen clear links emerge between the genetic determinants and neuropathological hallmarks of parkinsonism and dementia, notably with the discovery of mutations in alpha-synuclein and tau. Following the description of mutations in LRRK2 linked to Parkinson's disease, characterized by variable pathology including either alpha-synuclein or tau deposition, it has been suggested that LRRK2 functions as an upstream regulator of Parkinson's disease pathogenesis. This minireview explores this model, in the context of our current understanding of the biochemistry of LRRK2, alpha-synuclein and tau.
在过去十年中，帕金森病和痴呆症的遗传决定因素与神经病理学特征之间已出现明确的联系，尤其是随着α-突触核蛋白和tau基因突变的发现。在描述了与帕金森病相关的LRRK2基因突变后，其病理表现多样，包括α-突触核蛋白或tau蛋白沉积，有人提出LRRK2作为帕金森病发病机制的上游调节因子发挥作用。本综述在我们目前对LRRK2、α-突触核蛋白和tau蛋白生物化学理解的背景下探讨了这一模型。
