Targeting microglia L-type voltage-dependent calcium channels for the treatment of central nervous system disorders

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

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 languageEnglish (US)
Pages (from-to)141-162
Number of pages22
JournalJournal of Neuroscience Research
Volume99
Issue number1
DOIs
StatePublished - 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

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