مقاله انگلیسی رایگان در مورد تنظیم قطبیدگی یاخته بیگانه خوار با ویتامین ب3 در بیماری پارکینسون – الزویر 2018

Neuroinflammation remains a central piece in Parkinson’s disease (PD) pathophysiology. However, mechanisms by which PD links to the neuroinflammation remain elusive. Here, for the first time, we report that lower dose of niacin in PD patients may affect macrophage polarization from M1 (pro-inflammatory) to M2 (counter-inflammatory) profile through the niacin receptor GPR109A. Skew in the peripheral macrophages were accompanied by improved quality of life assessments in patients. Low dose niacin supplementation may be beneficial in PD, boosting anti-inflammatory processes and suppressing inflammation. Varied niacin dosages for longer durations may further reveal the potential role of anti-inflammatory interventions in PD progression.

Introduction

Parkinson’s disease is a progressive neurodegenerative disorder. Aging, genetic susceptibility and environmental factors play pivotal roles in its initiation, and progression. The main cause of PD still remains unknown and there is no cure (Moehle and West, 2015). Among all mechanisms and factors proposed to be involved in PD pathology, inflammation is universally thought to play a central role in the initiation and progression of PD (Moehle and West, 2015; Bartels et al., 2010). Acute inflammatory responses may initially be beneficial, however, chronic inflammation exacerbates brain damage. As a part of innate immunity, macrophages and neutrophils are known to cross the leaky blood brain barrier, secrete cytokines (e.g., interleukins, tumor necrosis factor, interferon gamma) that in turn can initiate and regulate inflammatory responses leading to neurodegenerative damage. Due to lineage proximity to microglia, macrophages have attracted increasing attention in relation to the onset and progression of PD (Moehle and West, 2015; Lee et al., 2017; Zhao et al., 2014). Macrophages can be divided into two classes of M1 (pro-inflammatory) and M2 (counterinflammatory) subtypes. The notion of macrophage polarization and skewing from M1 to M2 type may be a plausible modality in containing the chronic inflammation and slowing the progression of PD (Moehle and West, 2015). Our previous studies have demonstrated that niacin supplementation may influence the course of PD (Wakade et al., 2014; Wakade and Chong, 2014). Niacin can play a significant role in triggering and boosting anti-inflammatory immune responses in humans and animal models (Feingold et al., 2014). Niacin is a ligand for hydroxycarboxylic acid receptor 2 (HCAR2, also known as GPR109A). The counter inflammatory role of GPR109A has been already proposed (Salem and Wadie, 2017). Several studies have suggested that niacin’s effects maybe mediated via GPR109A/HCA2, which is highly expressed in adipose tissue and macrophages (Blad et al., 2012; Ganapathy et al., 2013; Singh et al., 2014a). Here in this study we demonstrated for the first time in PD patients, that niacin supplementation through its receptor, GPR109A, may alter the macrophages polarization from M1 to M2 profile. Most importantly, our findings indicated an improvement in quality of life for PD patients.