Neuroinflammation in Parkinson's disease

Abstract

During the last two decades, a wealth of animal and human studies has implicated inflammation-derived oxidative stress and cytokine-dependent neurotoxicity in the progressive degeneration of the dopaminergic nigrostriatal pathway, the hallmark of Parkinson's disease (PD). In this review, we discuss the various hypotheses regarding the role of microglia and other immune cells in PD pathogenesis and progression, the inflammatory mechanisms implicated in disease progression from pre-clinical and clinical studies, the recent evidence that systemic inflammation can trigger microglia activation in PD-relevant central nervous system regions, the synergism between gene products linked to parkinsonian phenotypes (alpha-synuclein, parkin, Nurr1, and regulator of G-protein signaling-10) and neuroinflammation in promoting neurodegeneration of the nigrostriatal pathway, and the latest update on meta-analysis of epidemiological studies on the risk-lowering effects of anti-inflammatory drug regimens.

Figures

Figure 1. Potential initiating factors of microglia activation in the CNS that contribute to progressive loss of nigral dopaminergic neurons and development of Parkinson’s disease (PD)

A number of different stimuli can activate microglia in the CNS. If the initiating trigger is left unresolved and/or with additional insults, chronic microglia activation contributes to an enhanced inflammatory environment in the brain. Chronic neuroinflammation results in enhanced oxidative stress on and/or chronic activation of cell death pathways in vulnerable neuronal populations (i.e. nigral dopaminergic neurons) and accelerated degeneration.