This review will highlight mitochondrial dysfunction as a common pathway involved in both genetic mutations and environmental toxicants linked to PD.
Parkinson’s disease (PD), characterized by degeneration of the nigrostriatal dopaminergic pathway, is the second most prevalent neurodegenerative disorder after Alzheimer’s disease. Manganese and calcium efflux kinetics in brain mitochondria.
The remaining cases have been attributed to other risk associated genes, environmental exposures and gene–environment interactions, making PD a multifactorial disorder with a complex etiology. doi: 10.1042/bj2660329 Cross Ref Full Text | Google Scholar Gavin, C.
However, enormous efforts from global research have yielded significant insights into pathogenic mechanisms and potential therapeutic targets for PD.
α-synuclein-associated mechanisms have therefore been at the forefront of the PD research and multiple high profile discoveries have greatly contributed to the understanding of disease pathology. Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter.
For example, as discussed below, the discovery that α-synuclein pathology can spread from one cell to another in a prion-like fashion has provided a key insight into how PD may develop and provide novel therapeutic strategies.
Duplications are more common than triplications, which has been found in several families (Hernandez et al., 2016). doi: 10.1046/j.1471-4159.1997.69031322.x Pub Med Abstract | Cross Ref Full Text | Google Scholar Gandhi, S., Wood-Kaczmar, A., Yao, Z., Plun-Favreau, H., Deas, E., Klupsch, K., et al. PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death.
α-synuclein is also understood to be a key factor of sporadic PD and present in Lewy bodies, which are abnormal proteins commonly observed in PD (Spillantini et al., 1998).
articles give insight into fundamental questions in current mutation research.
The feature considers mutation as broadly as possible, including its evolutionary, toxicological, medical, statistical, and public policy dimensions, as well as the basic genetics and molecular biology that form the core of mutation research.