Neurodegeneration and Neuroinflammation in Parkinson’s Disease: a Self-Sustained Loop

Abstract

Purpose of Review Neuroinflammation plays a significant role in Parkinson’s disease (PD) etiology along with mitochondrial dysfunction and impaired proteostasis. In this context, mechanisms related to immune response can act as modifiers at different steps of the neurodegenerative process and justify the growing interest in anti-inflammatory agents as potential disease-modifying treatments in PD. The discovery of inherited gene mutations in PD has allowed researchers to develop cellular and animal models to study the mechanisms of the underlying biology, but the original cause of neuroinflammation in PD is still debated to date. Recent Findings Cell autonomous alterations in neuronal cells, including mitochondrial damage and protein aggregation, could play a role, but recent findings also highlighted the importance of intercellular communication at both local and systemic level. This has given rise to debate about the role of non-neuronal cells in PD and reignited intense research into the gut-brain axis and other non-neuronal interactions in the development of the disease. Whatever the original trigger of neuroinflammation in PD, what appears quite clear is that the aberrant activation of glial cells and other components of the immune system creates a vicious circle in which neurodegeneration and neuroinflammation nourish each other. Summary In this review, we will provide an up-to-date summary of the main cellular alterations underlying neuroinflammation in PD, including those induced by environmental factors (e.g. the gut microbiome) and those related to the genetic background of affected patients. Starting from the lesson provided by familial forms of PD, we will discuss pathophysiological mechanisms linked to inflammation that could also play a role in idiopathic forms. Finally, we will comment on the potential clinical translatability of immunobiomarkers identified in PD patient cohorts and provide an update on current therapeutic strategies aimed at overcoming or preventing inflammation in PD.

The therapeutic potential of triptolide and celastrol in neurological diseases

“…Studies have shown that α-synuclein transmission is important in the pathogenesis of PD, which has made α-synuclein a hot topic in the field of PD research in recent years ( Kurowska et al, 2011 ; Ganguly et al, 2022 ). Moreover, research on neuroinflammation in the pathogenesis of PD has also received widespread attention ( Jenner and Olanow, 2006 ; Arena et al, 2022 ). As mentioned earlier, TWHF has anti-inflammatory properties.…”

Neuroinflammation in Parkinson’s Disease: From Gene to Clinic: A Systematic Review

“…The association of these organelles with α-syn is influenced by the polyphosphoinositide phosphatase SYNJ1 and group VI calcium-independent phospholipase A2, PLA2G6, which is involved in the control of lipid metabolism and located in these organelles. Lastly, these alterations lead to the overexpression of reactive oxygen species, thereby, promoting glial activation and neuroinflammation in a microenvironment of oxidative stress [ 47 , 48 , 49 ].…”

Effects of a probiotic suspension Symprove™ on a rat early-stage Parkinson’s disease model

“…Overall, treatment with the probiotic suspension prevented gut involvement in the model by maintaining a healthier GM, being able to avoid local and systemic inflammation, protecting gut integrity and improving SCFA production. As neuroinflammation is a major player in PD etiology, pathophysiology, and progression of the disease (Cicchetti et al, 2002;Doty, 2012;O'Neill and Harkin, 2018;Arena et al, 2022;Teleanu et al, 2022), the effect of Symprove™ on striatal neuroinflammation in the early-stage PD model was investigated in this study. Supplementation with the probiotics prevented activation of both astrocytes and microglia in the striatum that was observed in the early-stage PD model treated with placebo.…”

“…As neuroinflammation is a major player in PD etiology, pathophysiology, and progression of the disease ( Cicchetti et al, 2002 ; Doty, 2012 ; O'Neill and Harkin, 2018 ; Arena et al, 2022 ; Teleanu et al, 2022 ), the effect of Symprove™ on striatal neuroinflammation in the early-stage PD model was investigated in this study. Supplementation with the probiotics prevented activation of both astrocytes and microglia in the striatum that was observed in the early-stage PD model treated with placebo.…”