Fig. 2

Pathogenesis of synucleinopathies. LB is mainly formed in neurons, and it is composed of misfolded, fibrillar α-syn (α-synuclein). Different genes are associated with synucleinopathies, mutations of these genes induce α-syn aggregation, mitochondrial dysfunction, autophagy dysregulation, oxidative stress, and inflammation (Gene dysregulation). Immune cells in the periphery contribute to the pathogenesis of synucleinopathies. Innate and adaptive immune cells (monocytes and lymphocytes, respectively) migrate into the brain. Activated macrophages release pro-inflammatory cytokines (Immunity). This results in generalized microglia and astrocyte activation which leads to neuronal damage (Immunity and neuroinflammation). Abbreviations: LB; Lewy body, BBB: blood–brain barrier, CNS: central nervous system. The figure was created with BioRender.com