The involvement of alpha-synuclein in parkinson’s disease

Abstract

Parkinson’s disease (PD) is the second commonest neurodegenerative disease. Clinically, the disease is characterised by motor symptoms including resting tremor, and the loss of dopaminergic neurons in the substantia nigra. The histopathological hallmark of the disease is an inclusion body in the neuronal perikarya called Lewy body. The abnormal expression of alpha (α)-synuclein, a pre-synaptic neuronal protein, has been implicated as a biomarker of PDand is involvedin the pathogenesis of the disease. Amplification of the wild-type SNCA gene which encodes for α-synuclein, and its missense mutations lead to PD, thus implying that aberrant functions of the SNCA gene as well as its mutant expression are both capable of causing neurodegeneration. It is believed that α-synuclein contributes to the molecular pathological progression of PDin multiple ways. This article aims at reviewing the recent evidence pointing to the involvement of α-synuclein in the development of the neuropathological hallmarks associated withPD. By rationalising recent research findings on the aberrant expressions of α-synuclein, this review seeksto provide insights into the identified toxicities of this protein that may be targeted in the quest to design effective curative therapeutic interventions against the effects of the protein in PD.