Abstract
Calcium ions are vital for maintaining the physiological and biochemical processes inside cells. The central nervous system (CNS) is particularly dependent on calcium homeostasis and its dysregulation has been associated with several neurodegenerative disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD) and Huntington’s disease (HD), as well as with multiple sclerosis (MS). Hence, the modulation of calcium influx into the cells and the targeting of calcium-mediated signaling pathways may present a promising therapeutic approach for these diseases. This review provides an overview on calcium channels in neurons and glial cells. Special emphasis is put on MS, a chronic autoimmune disease of the CNS. While the initial relapsing-remitting stage of MS can be treated effectively with immune modulatory and immunosuppressive drugs, the subsequent progressive stage has remained largely untreatable. Here we summarize several approaches that have been and are currently being tested for their neuroprotective capacities in MS and we discuss which role calcium could play in this regard.
Highlights
Calcium is one of the most important second messengers regulating numerous cellular processes such as signal transduction, proliferation, muscle contraction and neurotransmitter release
It has been described that an increase in astrocytic intracellular calcium triggers the release of gliotransmitters like adenosine triphosphate (ATP), glutamate, D-serine and gamma-aminobutyric acid (GABA) [16]
This importance is reflected by numerous cellular processes which depend on calcium, and by the sheer amount of calcium-associated channels and receptors, which are expressed by various central nervous system (CNS) cell types
Summary
Calcium is one of the most important second messengers regulating numerous cellular processes such as signal transduction, proliferation, muscle contraction and neurotransmitter release. Astrocytes were first thought to be mainly important for providing passive structural support to neurons, but are well acknowledged to actively participate in the regulation of brain functions [12,13] They are part of the blood–brain barrier (BBB) [14] and are able to take up sodium and glutamate from the synaptic cleft following the initiation of an action potential [15]. Apart from neurons and glia, many other cells in the CNS depend on calcium It is clearly beyond the scope of this review to further elaborate on all calcium-mediated cellular processes, but it should be noted that, e.g., the permeability of the BBB, which consists of astrocytes and of endothelial cells and tight junctions, is regulated by intracellular calcium levels [18]. Other immune cells such as T cells, which physiologically populate the human brain, rely on calcium as a second messenger for intracellular processes [19]
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