It is becoming increasingly accepted that there is an interplay between the peripheral immune response and neuroinflammation in the pathophysiology of Parkinson’s disease (PD). Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene are associated with familial and sporadic cases of PD but are also found in immune-related disorders, such as inflammatory bowel disease (IBD) and leprosy. Furthermore, LRRK2 has been associated with bacterial infections such as Mycobacterium tuberculosis and Salmonella typhimurium. Recent evidence suggests a role of LRRK2 in the regulation of the immune system and modulation of inflammatory responses, at a systemic level, with LRRK2 functionally implicated in both the immune system of the central nervous system (CNS) and the periphery. It has therefore been suggested that peripheral immune signaling may play an important role in the regulation of neurodegeneration in LRRK2 as well as non-LRRK2-associated PD. This review will discuss the current evidence for this hypothesis and will provide compelling rationale for placing LRRK2 at the interface between peripheral immune responses and neuroinflammation.

中文翻译：

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LRRK2 位于帕金森病周围和中枢免疫功能之间的接口


人们越来越认识到，在帕金森病 (PD) 的病理生理学中，外周免疫反应和神经炎症之间存在相互作用。富含亮氨酸重复激酶 2 (LRRK2) 基因的突变与家族性和散发性 PD 病例相关，但也存在于免疫相关疾病中，例如炎症性肠病 (IBD) 和麻风病。此外，LRRK2 与结核分枝杆菌和鼠伤寒沙门氏菌等细菌感染有关。最近的证据表明 LRRK2 在系统水平上在免疫系统调节和炎症反应调节中发挥作用，其中 LRRK2 在功能上与中枢神经系统 (CNS) 和外周的免疫系统有关。因此，有人认为外周免疫信号传导可能在 LRRK2 以及非 LRRK2 相关 PD 神经变性的调节中发挥重要作用。这篇综述将讨论该假设的当前证据，并将为将 LRRK2 置于外周免疫反应和神经炎症之间的界面提供令人信服的理由。