The Role of Voltage-Gated Calcium Channels in Basal Ganglia Neurodegenerative Disorders

Abstract

Calcium (Ca²⁺) plays a central role in regulating many cellular processes and influences cell survival. Several mechanisms can disrupt Ca²⁺ homeostasis to trigger cell death, including oxidative stress, mitochondrial damage, excitotoxicity, neuroinflammation, autophagy, and apoptosis. Voltage-gated Ca²⁺ channels (VGCCs) act as the main source of Ca²⁺ entry into electrically excitable cells, such as neurons, and they are also expressed in glial cells such as astrocytes and oligodendrocytes. The dysregulation of VGCC activity has been reported in both Parkinson's disease (PD) and Huntington's (HD). PD and HD are progressive neurodegenerative disorders (NDs) of the basal ganglia characterized by motor impairment as well as cognitive and psychiatric dysfunctions. This review will examine the putative role of neuronal VGCCs in the pathogenesis and treatment of central movement disorders, focusing on PD and HD. The link between basal ganglia disorders and VGCC physiology will provide a framework for understanding the neurodegenerative processes that occur in PD and HD, as well as a possible path towards identifying new therapeutic targets for the treatment of these debilitating disorders.

Keywords: Calcium channels; basal ganglia and cell death; huntington’s disease; neurodegenerative disorders; parkinson’s disease.