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.

中文翻译：

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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。


钙 (Ca ²⁺ ) 是中枢神经系统 (CNS) 中多种细胞功能的普遍介质。细胞内Ca ²⁺受到细胞的严格调节，包括通过质膜Ca ²⁺渗透通道进入。本综述特别感兴趣的是 L 型电压依赖性 Ca ²⁺通道 (L-VDCC)，因为它们在多种中枢神经系统疾病中具有多效性作用。目前，有许多针对 L-VDCC 的批准药物，包括二氢吡啶。这些药物对于治疗人类心血管疾病是安全有效的，并且还可能具有神经保护作用。在这里，我们回顾了 L-VDCC 作为治疗中枢神经系统疾病的靶点的潜力，重点是小胶质细胞 L-VDCC。小胶质细胞是大脑的常驻免疫细胞，最近因其在多种中枢神经系统疾病中新兴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状态向“激活”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。我们将回顾有关中枢神经系统和小胶质细胞的体外和体内L-VDCC 表达和功能的文献，并探讨 L-VDCC 靶向药物目前的治疗前景以及阿尔茨海默病、帕金森病、亨廷顿舞蹈病、神经精神疾病和其他中枢神经系统疾病。