Alpha-synuclein and oxidative stress enzymes as biomarkers of Parkinson’s disease

Abstract

The principal mechanism of the pathogenesis of Parkinson’s disease is accumulation and aggregation of alpha-synuclein. While the normal function of alpha-synuclein is the control of vesicular neurotransmission, its pathogenic effects influence different cell functions, including the activities of mitochondria and proteasomes, as well as autophagic protein degradation. It is noteworthy that the same functions are affected when the renewal of macromolecules and organelles is impaired as a result of normal aging. Since aging is the principal risk factor for Parkinson’s disease, it is very important to analyze its molecular and cellular consequences in the context of alpha-synuclein pathology. Here, we review the similarities and differences between normal brain aging and Parkinson’s disease, with a focus on nigral dopaminergic neurons, which seem to be specifically sensitive to the combined damage induced by alpha-synuclein and aging. Elucidating the mechanism that underlies the death of dopaminergic neurons in Parkinson’s disease is essential not only for the understanding of its general pathogenesis but also for the development of approaches to its early preclinical diagnosis and preventive therapy.