Revisiting Alpha-Synuclein Pathways to Inflammation

Alpha-synuclein (alpha-Syn) is a short presynaptic protein with an active role on synaptic vesicle traffic and the neurotransmitter release and reuptake cycle. The alpha-Syn pathology intertwines with the formation of Lewy Bodies (multiprotein intraneuronal aggregations), which, combined with inflammatory events, define various alpha-synucleinopathies, such as Parkinson's Disease (PD). In this review, we summarize the current knowledge on alpha-Syn mechanistic pathways to inflammation, as well as the eventual role of microbial dysbiosis on alpha-Syn. Furthermore, we explore the possible influence of inflammatory mitigation on alpha-Syn. In conclusion, and given the rising burden of neurodegenerative disorders, it is pressing to clarify the pathophysiological processes underlying alpha-synucleinopathies, in order to consider the mitigation of existing low-grade chronic inflammatory states as a potential pathway toward the management and prevention of such conditions, with the aim of starting to search for concrete clinical recommendations in this particular population.

Automated summary

The development of neurodegenerative disorders, such as Parkinson's Disease, is closely linked to inflammation and dysbiosis. Understanding the mechanistic pathways of alpha-synucleinopathies and the impact of microbial dysbiosis on alpha-Syn can provide insights into the management and prevention of these conditions, with a focus on inflammatory mitigation and microbial balance.