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TITLE:

IMPACT OF LRRK2G2019S IN PRO-INFLAMMATORY CYTOKINES IN PARKINSON’S DISEASE PATIENTS

AUTHORS:

Dr. Asad Mumtaz, Dr. Adnan Mehmood, Dr. Hafiz Zafar Ullah

ABSTRACT:

PD is a neurodegenerative disorder, where the accumulation of α-SN aggregates is a central hallmark of the disease pathogenesis. However, the precise pathophysiological processes remain largely unidentified yet. Some of these genes seem to be particular relevant for the disease, including for example α-SN, glucocerebrosidase (GBA), parkin (PARK2), Pten-induced kinase 1 (PINK1), microtubule-associated protein tau (MAPT) and LRRK2. The LRRK2 is only gene discovered so far with familial and sporadic form of the PD. The clinically indistinguishable symptoms of the LRRK2 from the idiopathic form of the disease points towards the same pathogenic process. The prior studies focused on the role of monocytes involvement in the neuroinflamamtory process in the PD patients. However this study is first to study pro-inflammatory cytokines productions by classical and non-classical monocytes in idiopathic (PDI) and LRRK2(PDL) mutated groups of the PD. The trends towards increased production of pro-inflammatory cytokines in the LRRK2 mutated PD patients points towards a significant disease process in a PD patients. Our result concludes the increased production of pro-inflammatory cytokines in PDL patients in both classical and non-classical monocytes. This in consistence with the prior studies that showed increased cytokines production in the PD patients. Thus non-classical and classical monocytes could be useful biomarkers for detecting PD at early stage. Importantly presentation of the processed antigen by the macrophages activates the T-lymphocytes of the adaptive immunity that release cytokines to activate B-cells to generate immunoglobulin against the antigen. The antibodies produce by the Bcells can crossed the BBB and exert their influence via Fc receptors present in the microglia.Since blocking the Fc receptors present on the monocytes could halt the ongoing inflammatory process needs further research. In addition the influence of LRRK2 on the maturation B-lypmhocytes requires further studies as B-cells has high expression of LRRK2 after macrophages.

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