Voltage-Gated Ca²⁺ Channels in Dopaminergic Substantia Nigra Neurons: Therapeutic Targets for Neuroprotection in Parkinson's Disease?

ABSTRACT: The loss of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SN) underlies the core motor symptoms of the progressive movement disorder Parkinson's disease (PD). To date, no treatment to prevent or slow SN DA neurodegeneration exists; thus, the identification of the underlying factors contributing to the high vulnerability of these neurons represents the basis for the development of novel therapies. Disrupted Ca²⁺ homeostasis and mitochondrial dysfunction seem to be key players in the pathophysiology of PD. The autonomous pacemaker activity of SN DA neurons, in combination with low cytosolic Ca²⁺ buffering, leads to large somatodendritic fluctuations of intracellular Ca²⁺ levels that are linked to elevated mitochondrial oxidant stress.

SUBMITTER: Ortner NJ 

PROVIDER: S-EPMC7952618 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature