Targeting microglia L-type voltage-dependent calcium channels for the treatment of central nervous system disorders.
Targeting microglia L-type voltage-dependent calcium channels for the treatment of central nervous system disorders.
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靶向小胶质细胞L型电压依赖性钙通道治疗中枢神经系统疾病。
DOI：
10.1002/jnr.24585
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发表时间：
2021-01
影响因子：
4.2
通讯作者：
Hopp, Sarah C.
中科院分区：
文献类型：
--
作者：
Hopp, Sarah C.
关键词：
钙（Ca 2+）是中枢神经系统（CNS）多种细胞功能的普遍存在的介质。细胞内Ca 2+受细胞的严格调节，包括通过质膜Ca 2+渗透通道进入。特别感兴趣的是L型电压依赖性钙离子通道（L-VDCCs），由于其在几个中枢神经系统疾病的多效性作用。目前，有许多批准的药物靶向L-VDCC，包括二氢吡啶。这些药物对于治疗患有心血管疾病的人是安全有效的，并且还可以提供神经保护。在这里，我们回顾了L-VDCCs作为治疗CNS疾病的靶点的潜力，重点是小胶质细胞L-VDCCs。小胶质细胞是脑内的免疫细胞，近年来由于其在多种中枢神经系统疾病中的炎症作用而引起人们的关注。细胞内Ca 2+调节小胶质细胞从静止静止状态到“活化”免疫效应状态的转变，因此是操纵小胶质细胞表型的有价值的靶标。我们将回顾有关L-VDCC在CNS和小胶质细胞中的表达和功能的体外和体内文献，并探讨L-VDCC靶向药物在阿尔茨海默病、帕金森病、亨廷顿病、神经精神疾病和其他CNS疾病背景下的治疗前景和未来挑战。
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.
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影响因子：
4
作者：
Berridge, Michael J.
通讯作者：
Berridge, Michael J.
DOI：
10.1016/j.ijdevneu.2010.08.001
发表时间：
2011-02-01
影响因子：
1.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Gould, Todd D.
影响因子：
2.7
作者：
Braun, Moria D.;Kisko, Theresa M.;Woehr, Markus
通讯作者：
Woehr, Markus