Lyra, PatríciaMachado, VanessaRota, SilviaChaudhuri, Kallol RayBotelho, JoãoMendes, José João2026-03-112026-03-112023-04Lyra P, Machado V, Rota S, Chaudhuri KR, Botelho J, Mendes JJ. Revisiting Alpha-Synuclein Pathways to Inflammation. International Journal of Molecular Sciences. 2023; 24(8):7137. https://doi.org/10.3390/ijms240871371422-0067http://hdl.handle.net/10400.26/62123Alpha-synuclein (α-Syn) is a short presynaptic protein with an active role on synaptic vesicle traffic and the neurotransmitter release and reuptake cycle. The α-Syn pathology intertwines with the formation of Lewy Bodies (multiprotein intraneuronal aggregations), which, combined with inflammatory events, define various α-synucleinopathies, such as Parkinson’s Disease (PD). In this review, we summarize the current knowledge on α-Syn mechanistic pathways to inflammation, as well as the eventual role of microbial dysbiosis on α-Syn. Furthermore, we explore the possible influence of inflammatory mitigation on α-Syn. In conclusion, and given the rising burden of neurodegenerative disorders, it is pressing to clarify the pathophysiological processes underlying α-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.engalpha-synucleininflammationneuroinflammationsynucleinopathiesParkinson’s diseasecontribution to journal10.3390/ijms24087137