Abstract
Calcium (Ca2+) is a ubiquitous mediator of a multitude of cellular functions in the central nervous system (CNS). Intracellular Ca2+ is tightly regulated by cells, including entry via plasma membrane Ca2+ permeable channels. Of specific interest for this review are L-type voltage-dependent Ca2+ channels (L-VDCCs), due to their pleiotropic role in several CNS disorders. Currently, there are numerous approved drugs that target L-VDCCs, including dihydropyridines. These drugs are safe and effective for the treatment of humans with cardiovascular disease and may also confer neuroprotection. Here, we review the potential of L-VDCCs as a target for the treatment of CNS disorders with a focus on microglia L-VDCCs. Microglia, the resident immune cells of the brain, have attracted recent attention for their emerging inflammatory role in several CNS diseases. Intracellular Ca2+ regulates microglia transition from a resting quiescent state to an “activated” immune-effector state and is thus a valuable target for manipulation of microglia phenotype. We will review the literature on L-VDCC expression and function in the CNS and on microglia in vitro and in vivo and explore the therapeutic landscape of L-VDCC-targeting agents at present and future challenges in the context of Alzheimer's disease, Parkinson's disease, Huntington's disease, neuropsychiatric diseases, and other CNS disorders.
Original language | English (US) |
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Pages (from-to) | 141-162 |
Number of pages | 22 |
Journal | Journal of Neuroscience Research |
Volume | 99 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2021 |
Keywords
- Alzheimer's disease
- CACNA1C
- CACNA1D
- Cav1.2
- Cav1.3
- Huntington's disease
- L-type voltage-dependent calcium channels
- Parkinson's disease
- aging
- bipolar disorder
- calcium
- depression
- microglia
- neuroinflammation
- neuropsychiatric diseases
- schizophrenia
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience