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

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.

Automated summary

Calcium (Ca2+) is crucial for cellular regulation and cell survival, but disruptions in Ca2+ homeostasis can lead to cell death. Voltage-gated Ca2+ channels (VGCCs) are the main source of Ca2+ entry into cells, and their dysregulation has been implicated in Parkinson's disease (PD) and Huntington's disease (HD). This review focuses on the role of neuronal VGCCs in the pathogenesis and treatment of PD and HD, aiming to understand the neurodegenerative processes and identify potential therapeutic targets.