Neuroinflammation in Parkinson's disease and its potential as therapeutic target.

Qinqin Wang,Yingjun Liu,Jiawei Zhou

doi:10.1186/s40035-015-0042-0

Abstract

Parkinson’s disease (PD), the second most common age-associated neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons and the presence of α-synuclein-containing aggregates in the substantia nigra pars compacta (SNpc). Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Post-mortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain. Chronic release of pro-inflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc. Besides, peripheral immune system is also implicated in the pathogenesis of PD. Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients. Moreover, inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases. A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies. In this review, we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.

Highlights

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized clinically by resting tremor, slowness of movement, rigidity and postural instability and pathologically by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) [1,2,3,4]
Emerging evidence indicates that sustained inflammatory responses, T cell infiltration and glial cell activation are common features of both human PD patients and animal models of PD and play vital roles in the degeneration of DA neurons [9, 10], which suggests the possibility of developing potential therapies for PD by targeting the inflammatory processes
The idea that Drd2 plays important roles in the modulation of neuroinflammation is supported by a recent study in which Drd2 activation by Drd2 agonists quinpirole and ropinirole reduces expression levels of IL-1β and monocyte chemoattractant protein-1 as well as microglia/ macrophages activation in experimental intracerebral hemorrhage brain injury model [60]. These results further suggest the anti-inflammatory effects of Drd2 in certain central nervous system (CNS) disorders

Summary

Introduction

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized clinically by resting tremor, slowness of movement, rigidity and postural instability and pathologically by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) [1,2,3,4]. Emerging evidence indicates that sustained inflammatory responses, T cell infiltration and glial cell activation are common features of both human PD patients and animal models of PD and play vital roles in the degeneration of DA neurons [9, 10], which suggests the possibility of developing potential therapies for PD by targeting the inflammatory processes. Deficiency of CX3CL1 or CX3CR1 in vivo results in increased neurotoxicity induced by systemic lipopolysaccharide (LPS) treatment and enhanced cell death of DA neurons in the SNpc of animal PD models [28, 29].

Results

Conclusion