Neuroinflammation and parkinson's disease

Abstract

Parkinson's disease (PD) is characterized by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. To date, despite an intensive research, the cause of the neuronal loss in PD is poorly understood. It has been postulated that neuroinflammatory mechanisms might contribute to the cascade of events leading to this neuronal degeneration. In this review, we describe the evidence for neuroinflammatory processes from postmortem, in vivo and in vitro studies in PD. We further identify the cellular types associated with neuroinflammation that are involved in the degeneration of dopaminergic neurons in animal models and PD patients. Overall, available data support the importance of non-cell-autonomous pathological mechanisms in PD, which are mostly mediated by activated glial and peripheral immune cells. This cellular response to neurodegeneration triggers deleterious events (e.g., oxidative stress and cytokine-receptor-mediated apoptosis), which might eventually lead to dopaminergic cell death and hence disease progression. Novel studies have also demonstrated that genetic markers could be implicated in neuroinflammation and even in the role of glucocorticoids in sustaining activated microglia in inflammatory processes. Finally, based on these evidences, we highlight possible therapeutic strategies aimed at downregulating these inflammatory processes that might be important to slow down the progression of PD.