Relationship among α-synuclein, aging and inflammation in Parkinson's disease (Review)

Parkinson's disease (PD) is a common neurodegenerative pathology whose major clinical symptoms are movement disorders. The main pathological characteristics of PD are the selective death of dopaminergic (DA) neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing alpha-synuclein (alpha-Syn) within these neurons. PD is associated with numerous risk factors, including environmental factors, genetic mutations and aging. In many cases, the complex interplay of numerous risk factors leads to the onset of PD. The mutated alpha-Syn gene, which expresses pathological alpha-Syn protein, can cause PD. Another important feature of PD is neuroinflammation, which is conducive to neuronal death. alpha-Syn is able to interact with certain cell types in the brain, including through phagocytosis and degradation of alpha-Syn by glial cells, activation of inflammatory pathways by alpha-Syn in glial cells, transmission of alpha-Syn between glial cells and neurons, and interactions between peripheral immune cells and alpha-Syn. In addition to the aforementioned risk factors, PD may also be associated with aging, as the prevalence of PD increases with advancing age. The aging process impairs the cellular clearance mechanism, which leads to chronic inflammation and the accumulation of intracellular alpha-Syn, which results in DA neuronal death. In the present review, the age-associated alpha-Syn pathogenicity and the interactions between alpha-Syn and certain types of cells within the brain are discussed to facilitate understanding of the mechanisms of PD pathogenesis, which may potentially provide insight for the future clinical treatment of PD.