The Involvement of Neuroinflammation in the Onset and Progression of Parkinson’s Disease

Abstract

Parkinson’s disease is a neurodegenerative disease exhibiting the fastest growth in incidence in recent years. As with most neurodegenerative diseases, the pathophysiology is incompletely elucidated, but compelling evidence implicates inflammation, both in the central nervous system and in the periphery, in the initiation and progression of the disease, although it is not yet clear what triggers this inflammatory response and where it begins. Gut dysbiosis seems to be a likely candidate for the initiation of the systemic inflammation. The therapies in current use provide only symptomatic relief, but do not interfere with the disease progression. Nonetheless, animal models have shown promising results with therapies that target various vicious neuroinflammatory cascades. Translating these therapeutic strategies into clinical trials is still in its infancy, and a series of issues, such as the exact timing, identifying biomarkers able to identify Parkinson’s disease in early and pre-symptomatic stages, or the proper indications of genetic testing in the population at large, will need to be settled in future guidelines.

The Impact of Intestinal Microbiota and Toll-like Receptor 2 Signaling on α-Synuclein Pathology in Nontransgenic Mice Injected with α-Synuclein Preformed Fibrils

“…Various pathways have been reported as mechanisms by which intestinal microbiota and TLR2 signaling affect α-synuclein accumulation in PD [ 44 ]. Studies have shown that microglial activation in PD pathology can induce the accumulation of α-synuclein aggregates and the degeneration of dopaminergic neurons in the substantia nigra [ 45 , 46 ].…”

Microbiota, Tryptophan and Aryl Hydrocarbon Receptors as the Target Triad in Parkinson’s Disease—A Narrative Review

“…On the other hand, certain microbiota-derived antigens and metabolites can promote a “leaky gut” syndrome and elicit intestinal inflammation. It is currently acknowledged that peripheral inflammation is a potential risk factor in various neurodegenerative diseases, especially PD (for a review, see [ 10 , 32 , 33 , 34 ]). Reactive microgliosis within the SN, an increased number of major histocompatibility complex (MHC) II-positive cells in various brain areas and high levels of pro-inflammatory molecules are hallmarks of PD [ 10 ].…”

“…It is currently acknowledged that peripheral inflammation is a potential risk factor in various neurodegenerative diseases, especially PD (for a review, see [ 10 , 32 , 33 , 34 ]). Reactive microgliosis within the SN, an increased number of major histocompatibility complex (MHC) II-positive cells in various brain areas and high levels of pro-inflammatory molecules are hallmarks of PD [ 10 ]. Furthermore, sustained activation of the immune system, manifested by increased levels of cytokines and chemokines, is evident in the blood and gut of PD patients [ 10 ].…”

“…Substantial experimental data obtained in animal models of PD revealed prominent microglial activation and other inflammatory changes preceding dopaminergic neuronal loss [ 35 ]. Such changes were detected in models evoked by intracerebral administration of neurotoxin 6-hydroxydopamine (6-OHDA), systemic application of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; mitochondrial toxin) or paraquat (pesticide) and oral treatment with rotenone (a naturally occurring pesticide and insecticide) [ 10 , 36 ].…”

“…Cellular and molecular pathways leading to neuronal loss are complex and involve, among others, mitochondrial dysfunction, impaired regulation of the proteome, excitotoxicity or neuroinflammation. Since the pathogenesis of PD has been the subject of a number of timely reviews recently (see, for example, [ 8 , 9 , 10 ]), it will not be presented here in detail.…”