α‐Synuclein in Parkinson's Disease: From Bench to Bedside

ABSTRACT α‐Synuclein (α‐syn), a pathological hallmark of PD, is emerging as a bridging element at the crossroads between neuro/immune‐inflammatory responses and neurodegeneration in PD. Several evidence show that pathological α‐syn accumulates in neuronal and non‐neuronal cells (i.e., neurons, microglia, macrophages, skin cells, and intestinal cells) in central and peripheral tissues since the prodromal phase of the disease, contributing to brain pathology. Indeed, pathological α‐syn deposition can promote neurogenic/immune‐inflammatory responses that contribute to systemic and central neuroinflammation associated with PD. After providing an overview of the structure and functions of physiological α‐syn as well as its pathological forms, we review current studies about the role of neuronal and non‐neuronal α‐syn at the crossroads between neuroinflammation and neurodegeneration in PD. In addition, we provide an overview of the correlation between the accumulation of α‐syn in central and peripheral tissues and PD, related symptoms, and neuroinflammation. Special attention was paid to discussing whether targeting α‐syn can represent a suitable therapeutical approach for PD.