Are ion channels potential therapeutic targets for Parkinson's disease?

Parkinson's disease (PD) is primarily associated with the progressive neurodegeneration of the dopaminergic neurons in the substantia nigra region of the brain. The resulting motor symptoms are managed with the help of dopamine replacement therapies. However, these therapeutics do not prevent the neurodegeneration underlying the disease and therefore lose their effectiveness in managing disease symptoms over time. Thus, there is an urgent need to develop newer therapeutics for the benefit of patients. The release of dopamine and the firing activity of substantia nigra neurons is regulated by several ion channels that act in concert. Dysregulations of these channels cause the aberrant movement of various ions in the intracellular milieu. This eventually leads to disruption of intracellular signalling cascades, alterations in cellular homeostasis, and bioenergetic deficits. Therefore, ion channels play a central role in driving the high vulnerability of dopaminergic neurons to degenerate during PD. Targeting ion channels offers an attractive mechanistic strategy to combat the process of neurodegeneration. In this review, we highlight the evidence pointing to the role of various ion channels in driving the PD processes. In addition, we also discuss the various drugs or compounds that target the ion channels and have shown neuroprotective potential in the in-vitro and in-vivo models of PD. We also discuss the current clinical status of various drugs targeting the ion channels in the context of PD.