The role of voltage-gated calcium channels in the pathogenesis of Parkinson's disease

Aim: Voltage-gated calcium (Ca-V) channels play an essential role in maintaining calcium homeostasis and regulating numerous physiological processes in neurons. Therefore, dysregulation of calcium signaling is relevant in many neurological disorders, including Parkinson's disease (PD). This review aims to introduce the role of Ca-V channels in PD and discuss some novel aspects of channel regulation and its impact on the molecular pathophysiology of the disease. Methods: an exhaustive search of the literature in the field was carried out using the PubMed database of The National Center for Biotechnology Information. Systematic searches were performed from the initial date of publication to May 2022. Results: Although alpha-synuclein aggregates are the main feature of PD, L-type calcium (Ca(V)1) channels seem to play an essential role in the pathogenesis of PD. Changes in the functional expression of Ca(V)1.3 channels alter Calcium homeostasis and contribute to the degeneration of dopaminergic neurons. Furthermore, recent studies suggest that Ca-V channel trafficking towards the cell membrane depends on the activity of the ubiquitin-proteasome system (UPS). In PD, there is an increase in the expression of L-type channels associated with a decrease in the expression of Parkin, an E3 enzyme of the UPS. Therefore, a link between Parkin and Ca-V channels could play a fundamental role in the pathogenesis of PD and, as such, could be a potentially attractive target for therapeutic intervention. Conclusion: The study of alterations in the functional expression of Ca-V channels will provide a framework to understand better the neurodegenerative processes that occur in PD and a possible path toward identifying new therapeutic targets to treat this condition.