钙是一种普遍存在的第二信使,在调节神经传递和记忆形成中是必不可少的。精确的细胞内钙水平是通过钙通道的协同作用来实现的,钙通过与一系列钙结合蛋白结合而发挥作用,包括钙调蛋白(CAM),钙-钙调蛋白复合物依赖性蛋白激酶-II(CAMK-II),Calbindin(CAL),和钙调磷酸酶(CAN)。Calbindin协调了调节突触传递和去极化信号的过多信号事件。维生素D,内源性脂溶性代谢物,在暴露于紫外线B辐射后在皮肤中合成。它通过增加钙敏感受体(CaSR)的表达来调节钙信号,刺激磷脂酶C活性,并调控TRPV6等钙通道的表达。维生素D还调节钙结合蛋白的活性,包括CAM和calbindin,增加他们的表达。Calbindin,一种高亲和力的钙结合蛋白,参与神经元的钙缓冲和运输。已显示其抑制AD中早老素1和2刺激的细胞凋亡和caspase-3活性。而CAM,另一种钙结合蛋白,与通过磷酸化CAN调节神经递质释放和记忆形成有关,CAMK-II,和其他钙调节蛋白。CAMK-II和CAN调节肌动蛋白诱导的脊柱形状变化,由CAM进一步调制。钙结合蛋白和维生素D的低水平归因于阿尔茨海默病的病理。通过钙结合蛋白-CAMK-II信号传导对维生素D的进一步研究可能会提供新的见解,揭示新的治疗靶点和治疗策略。
Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II),
calbindin (CAL), and calcineurin (CAN).
Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression.
Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both
calbindin and vitamin D are attributed to the pathology of Alzheimer\'s disease. Further research on vitamin D via
calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.