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Abstract：
Pathological mutations in the LRRK2 gene are the major genetic cause of Parkinson\'s disease (PD). Although several animal models with either LRRK2 down- or over-expression have been developed, the physiological function of LRRK2 remains elusive. LRRK2 is constitutively expressed in various tissues including neurons and glial cells, but importantly, it is expressed at low levels in dopaminergic neurons, further contributing to the cryptic function of LRRK2. Significant levels of LRRK2 protein and mRNA have been detected in peripheral blood mononuclear cells, lymph nodes, the spleen, and primary microglia, strongly suggesting the contribution of inflammatory cells to neuronal degeneration. In this research article, using Drosophila LRRK2 models, we were able to demonstrate a significant contribution of glial cells to the LRRK2 pathological phenotype. Furthermore, in Drosophila, neurodegeneration is associated with a significant and important increase in specific inflammatory peptides. Finally, levetiracetam, a compound widely used in human therapy to treat epilepsy, was able to rescue both neuronal degeneration and neuroinflammation.
摘要：
LRRK2基因的病理突变是帕金森病(PD)的主要遗传原因。尽管已经开发了几种LRRK2低表达或过表达的动物模型，LRRK2的生理功能仍然难以捉摸。LRRK2在各种组织中组成型表达，包括神经元和神经胶质细胞，但重要的是,它在多巴胺能神经元中低水平表达，进一步有助于LRRK2的神秘功能。在外周血单核细胞中检测到显著水平的LRRK2蛋白和mRNA，淋巴结,脾脏,和原发性小胶质细胞，强烈暗示炎症细胞对神经元变性的贡献。在这篇研究文章中，使用果蝇LRRK2模型，我们能够证明神经胶质细胞对LRRK2病理表型的重要贡献。此外，在果蝇中，神经变性与特定炎症肽的显著和重要增加有关。最后,左乙拉西坦,一种广泛用于人类治疗癫痫的化合物，能够挽救神经元变性和神经炎症。
