Targeting microglia L-type voltage-dependent calcium channels for the treatment of central nervous system disorders.
J Neurosci Res
; 99(1): 141-162, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-31997405
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças do Sistema Nervoso Central
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Microglia
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Canais de Cálcio Tipo L
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Neurosci Res
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos