Published in:
Open Access
01-12-2016 | Letter to the Editor
LRRK2 contributes to monocyte dysregulation in Parkinson’s disease
Authors:
Corinna Bliederhaeuser, Lisa Zondler, Veselin Grozdanov, Wolfgang P. Ruf, David Brenner, Heather L. Melrose, Peter Bauer, Albert C. Ludolph, Frank Gillardon, Jan Kassubek, Jochen H. Weishaupt, Karin M. Danzer
Published in:
Acta Neuropathologica Communications
|
Issue 1/2016
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Excerpt
Mutations in the
leucine-rich repeat kinase 2 (
LRRK2) gene are the most common cause of familial Parkinson’s disease (PD) [
20,
32]. Common polymorphisms in
LRRK2 have been shown to modulate the risk for sporadic PD [
6,
23,
24] strengthening the idea that inherited and sporadic PD share common underlying pathways. Although LRRK2 has been associated with a variety of cellular functions, including autophagy [
1], mitochondrial function/dynamics [
30] and microtubule/cytoskeletal dynamics [
12], the overall physiological function of LRRK2 and its role in PD are only partially understood. Relatively recent studies also support a role for LRRK2 as regulator of inflammation. Substantial levels of LRRK2 protein and mRNA have been reported in immune cells like peripheral blood mononuclear cells (PBMCs), including B-cells, monocytes/macrophages, and dendritic cells [
9,
13,
16,
29]. Moreover, LRRK2 has been shown to be involved in the activation and maturation of immune cells [
29], in controlling the radical burst against pathogens in macrophages [
9] and in modulating neuroinflammation by cytokine signaling [
10,
19]. Remarkably, elevated levels of serum cytokines (IL-2, IL-4, IL-6, IL-10, TNFα) in PD patients [
4,
22,
27] point to an involvement of the peripheral immune system in the pathogenesis of PD. Recently, we found an enrichment of “classical” CD14
++CD16
− monocyte subpopulation in the peripheral blood of PD patients together with a dysregulation of inflammatory pathways, phagocytosis deficits as well as hyperactivation of PD monocytes in response to LPS treatment, which correlated to PD severity [
11]. Here, we sought to study the contribution of LRRK2 to the dysregulation of monocytes in Parkinson’s disease. …