New therapeutic approaches to target alpha-synuclein in Parkinson's disease: The role of immunotherapy.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by a slow and progressive loss of dopaminergic neurons. Its neuropathological hallmark is the accumulation of aggregated form of α-synuclein (α-syn) protein in intracellular inclusions known as Lewy bodies. This aggregated α-syn is believed to be central to the pathogenesis of PD. Emerging evidence suggests that aggregated forms of α-syn self-amplificates and propagates spreading from cell-to-cell in a "prion-like" fashion. Genetics and environmental factors are known causes for the pathogenesis of PD. In last years, inflammation in the pathophysiology of PD is gaining more importance. This neuroinflammation seems to contribute to the progressive degeneration of dopaminergic neurons. The currently available therapies for PD fail to modify the disease progression and neurodegeneration. The connection between α-syn and PD makes α-syn the major therapeutic target. We summarize the possible therapeutic strategies to target α-syn according to the steps in the molecular pathogenesis. The contribution of neuroinflammation to the progression of the disease and the "prion-like" hypothesis which enables targeting the extracellular phase of transmission of α-syn, make immunotherapy probably the most promising therapeutic approach for PD.