title: Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease.
abstract: Idiopathic Parkinson's disease (PD) represents a complex interaction between the inherent vulnerability of the nigrostriatal dopaminergic system, a possible genetic predisposition, and exposure to environmental toxins including inflammatory triggers. Evidence now suggests that chronic neuroinflammation is consistently associated with the pathophysiology of PD. Activation of microglia and increased levels of pro-inflammatory mediators such as TNF-α, IL-1β and IL-6, reactive oxygen species and eicosanoids has been reported after post-mortem analysis of the substantia nigra from PD patients and in animal models of PD. It is hypothesised that chronically activated microglia secrete high levels of pro-inflammatory mediators which damage neurons and further activate microglia, resulting in a feed forward cycle promoting further inflammation and neurodegeneration. Moreover, nigrostriatal dopaminergic neurons are more vulnerable to pro-inflammatory and oxidative mediators than other cell types because of their low intracellular glutathione concentration. Systemic inflammation has also been suggested to contribute to neurodegeneration in PD, as lymphocyte infiltration has been observed in brains of PD patients and in animal models of PD, substantiating the current theory of a fundamental role of inflammation in neurodegeneration. We will examine the current evidence in the literature which offers insight into the premise that both central and systemic inflammation may contribute to neurodegeneration in PD. We will discuss the emerging possibility of the use of diagnostic tools such as imaging technologies for PD patients. Finally, we will present the immunomodulatory therapeutic strategies that are now under investigation and in clinical trials as potential neuroprotective drugs for PD.
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Biosciences Institute, Western Road, Cork, Ireland.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Collins
authors.forename: André
authors.initials: A
authors.lastname: Toulouse
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Connor
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Nolan
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D018836:Inflammation Mediators