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

Abstract

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 α-synuclein (α-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 α-Syn gene, which expresses pathologicalα-Syn protein, can cause PD. Another important feature of PD is neuroinflammation, which is conducive to neuronal death. α-Syn is able to interact with certain cell types in the brain, including through phagocytosis and degradation of α-Syn by glial cells, activation of inflammatory pathways by α-Syn in glial cells, transmission of α-Syn between glial cells and neurons, and interactions between peripheral immune cells and α-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 α-Syn, which results in DA neuronal death. In the present review, the age-associated α-Syn pathogenicity and the interactions between α-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.

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“…Missense mutations in the SNCA genes (A53T, A53E, H50Q, G51D, E46K, and A30P) have been reported through genetic testing in patients with early-onset PD [ 45 ]. In the brain, α-Syn can interact with specific cell types through a variety of mechanisms, such as glial cell phagocytosis and degradation of α-Syn, glial cell activation of inflammatory pathways, α-Syn transmission between glial cells and neurons, and interactions with peripheral immune cells [ 46 ]. These findings have raised the possibility that α-Syn plays a role in the development of familial PD.…”