Evidence of inflammatory system involvement in Parkinson's disease.

Yinxia Chao,Eng King Tan,Siew Cheng Wong

doi:10.1155/2014/308654

Abstract

Parkinson's disease (PD) is a chronic neurodegenerative disease underpinned by both genetic and environmental etiologic factors. Recent findings suggest that inflammation may be a pathogenic factor in the onset and progression of both familial and sporadic PD. Understanding the precise role of inflammatory factors in PD will likely lead to understanding of how the disease arises. In vivo evidence for inflammation in PD includes dysregulated molecular mediators such as cytokines, complement system and its receptors, resident microglial activation, peripheral immune cells invasion, and altered composition and phenotype of peripheral immune cells. The growing awareness of these factors has prompted novel approaches to modulate the immune system, although it remains whether these approaches can be used in humans. Influences of ageing and differential exposure to environmental agents suggest potential host-pathogen specific pathophysiologic factors. There is a clear need for research to further unravel the pathophysiologic role of immunity in PD, with the potential of developing new therapeutic targets for this debilitating condition.

Highlights

Parkinson’s disease (PD), characterized by a loss of dopaminergic neuron, is a common movement disorder, affecting over 4 million individuals worldwide
Research on susceptibility genes identified by GWAS indicates that some autoimmune diseases such as Crohn’s disease may share mutations on the same gene LRRK2, which has exemplified the significance of immune system in the pathogenesis of PD
We propose that the likelihood of a common mechanism fundamental to the etiology of all genetic backgrounds of PD is the dysregulation of the immune system, which makes the patients vulnerable to environmental challenge, such as infections or chemical exposure

Summary

Introduction

Parkinson’s disease (PD), characterized by a loss of dopaminergic neuron, is a common movement disorder, affecting over 4 million individuals worldwide. Several genes have been identified including SNCA, PARKIN, DJ-1, PINK1, and LRRK2, whose mutations are responsible for rare familial forms of PD. Despite such progress, the functions of the products of most susceptibility genes have not been fully elucidated. Research on susceptibility genes identified by GWAS indicates that some autoimmune diseases such as Crohn’s disease may share mutations on the same gene LRRK2, which has exemplified the significance of immune system in the pathogenesis of PD. Manzanillo and colleagues have shown that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis They reported that both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections [5]. We review the involvement of immune system (Figure 1) and inflammatory factors (Table 1) in the pathogenesis of PD and discuss potential therapeutic targets of immune regulation in PD

Molecular Mediators

Peripheral Leukocyte Infiltration

PD and Infectious Disease

Immune Regulation as Therapeutic Targets

Findings

Conclusions