Potential Alternative Inhibitors of Alpha-Synuclein and Effective Treatment of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the second common prevalent progressive neurodegenerative disorder mainly affecting the elderly. The disease gradually exhibits symptoms from resting tremor, bradykinesia, rigidity, and postural instability. Misfolding and aggregation of alpha-synuclein is considered the main pathological hallmark of the disease. Currently, treatment options for PD are only symptom-targeted, while an effective therapeutic strategy remains a challenge. Therefore, this study aims to comprehensively review α-synuclein, its implications and unique structural features as an effective therapeutic target for PD treatment. The earmarked structural modifications of the protein target in the pathogenesis of the disease include aggregation, propagation, and misfolding, while inhibitions of formation and propagation of monomers, oligomers and fibrils are essentially implicated as pharmacological pathways. Through experimental studies such as enzyme-linked immunosorbent assay (ELISA), Luminex, and thioflavin T (ThT) assay, potent inhibitors such as myricetin, curcumin, crocin, nanobodies including VH14*PEST, and NbSyn87*PES are notably identified as therapeutic alternatives and can be subjected to computational study and derivatized to obtained new molecules that could be of therapeutic value. The review highlights important critical implications of α-synuclein in the pathogenesis of PD and some therapeutic potentials against PD that is amenable for further translational study.