Calcium Signaling Pathways in Physiological Regulation and Disease Development: A Comprehensive Review
DOI:
https://doi.org/10.48048/tis.2026.12261Keywords:
Calcium signaling, Physiology, Pathology, Targeted therapy, DiseaseAbstract
Calcium ions (Ca²⁺) are universal signaling molecules that play a central role in physiological processes, including muscle contraction, hormone secretion, gene regulation, energy metabolism, and neurotransmission. This review aims to integrate the SOCE-MCU-CaM axes to provide a systems-level view of Ca²⁺ regulation from the plasma membrane to the ER/SR, mitochondria, and nucleus in physiology and pathology. The Ca²⁺ signaling pathway encompasses ion transport by Ca²⁺ pumps and Na⁺/Ca²⁺ exchangers, ion flow through plasma-membrane channels and the endoplasmic/sarcoplasmic reticulum (ER/SR), and interactions with binding proteins such as calcineurin and calmodulin (CaM), which trigger downstream programs including NFAT, CREB, and MAPK. Maintenance of cytosolic and mitochondrial Ca²⁺ homeostasis depends on pathways such as the mitochondrial calcium uniporter (MCU) and store-operated calcium entry (SOCE) via STIM1/Orai1; their coordinated action links Ca²⁺ transients to metabolism and gene control. Dysregulation of Ca²⁺ signaling contributes to chronic diseases, including neurodegeneration (Alzheimer’s, Parkinson’s), cardiovascular disease (heart failure, arrhythmia, hypertension), cancer (breast, lung, colorectal), and metabolic/endocrine disorders (diabetes and insulin resistance). Unchecked Ca²⁺ accumulation or pathway imbalance promotes oxidative stress, apoptotic activation, impaired energy metabolism, and cellular dysfunction, while mutations in Ca²⁺-related genes alter cardiac contractility and other physiological regulation. Therapeutic approaches include Ca²⁺-channel modulation, targeting STIM1, Orai1, and MCU, and epigenetic strategies that leverage Ca²⁺’s influence on gene expression, with the goal of restoring network-level Ca²⁺ equilibrium and improving cell function. A clearer understanding of Ca²⁺ mechanisms and pathway cross-talk will support the development of more precise and effective interventions.
HIGHLIGHTS
- Homeostatic Ca²⁺ signaling integrates SOCE (STIM1-Orai1), VGCCs, SERCA/PMCA, and mitochondrial MCU to coordinate excitation-secretion, metabolism, and gene programs.
- Organellar Ca²⁺ dysregulation underlies neurodegeneration, cardiac remodeling/arrhythmia, endocrine-metabolic dysfunction, and cancer progression.
- Calmodulin-driven transduction (CaM-calcineurin/NFAT and CaMK axes) links Ca²⁺ oscillations to transcriptional remodeling and disease-specific vulnerabilities.
- Mitochondrial Ca²⁺ uptake via the MCU complex couple’s bioenergetics to redox signaling; imbalance promotes ROS, defective mitophagy, and cell death.
- Therapeutic avenues span SOCE inhibitors and selective Ca²⁺ channel blockers to mitochondria-targeted MCU modulators with disease-tailored strategies.
- Research priorities: Cell-type-resolved Ca²⁺ mapping with advanced imaging and multi-omics to identify precision targets along SOCE-MCU-CaM pathways.
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P Köster, TA DeFalco and C Zipfel. Ca²⁺ signals in plant immunity. The EMBO Journal 2022; 41(12), e110741.
G Bkaily and D Jacques. Calcium homeostasis, transporters, and blockers in health and diseases of the cardiovascular system. International Journal of Molecular Sciences 2023; 24(10), 8803.
R Bagur and G Hajnóczky. Intracellular Ca²⁺ sensing: Its role in calcium homeostasis and signaling. Molecular Cell 2017; 66(6), 780-788.
C Dai and RA Khalil. Calcium signaling dynamics in vascular cells and their dysregulation in vascular disease. Biomolecules 2025; 15(6), 892.
E Murphy and JC Liu. Mitochondrial calcium and reactive oxygen species in cardiovascular disease. Cardiovascular Research 2023; 119(5), 1105-1116.
G Bastioli, S Piccirillo, L Graciotti, M Carone, G Sprega, O Taoussi, A Preziuso and P Castaldo. Calcium deregulation in neurodegeneration and neuroinflammation in Parkinson’s disease: Role of calcium-storing organelles and sodium-calcium exchanger. Cells 2024; 13(15), 1301.
I Shemarova. The dysfunction of Ca²⁺ channels in hereditary and chronic human heart diseases and experimental animal models. International Journal of Molecular Sciences 2023; 24(21), 15682.
J Zhu, P Xun, JC Bae, JH Kim, DJ Kim, K Yang and K He. Circulating calcium levels and the risk of type 2 diabetes: a systematic review and meta-analysis. British Journal of Nutrition 2019; 122(4), 376-387.
RP Ureshino, AG Erustes, TB Bassani, P Wachilewski, GC Guarache, AC Nascimento, AJ Costa, SS Smaili and GJDS Pereira. The interplay between Ca²⁺ signaling pathways and neurodegeneration. International Journal of Molecular Sciences 2019; 20(23), 6004.
S Ramos, J Gregório, AS Fernandes and N Saraiva. Association between dysregulated expression of Ca²⁺ and ROS-related genes and breast cancer patient survival. Frontiers in Bioinformatics 2025; 5(1), 1633494.
A Wdowiak, A Podgórska and B Szal. Calcium in plants: An important element of cell physiology and structure, signaling, and stress responses. Acta Physiologiae Plantarum 2024; 46(1), 108.
WA Catterall. Voltage-gated calcium channels. Cold Spring Harbor Perspectives in Biology 2011; 3(8), a003947.
HO Gu, SW Noh, OH Kim and BC Oh. Crucial roles of calcium ATPases and phosphoinositides: Insights into pathophysiology and therapeutic strategies. Molecules and Cells 2025; 48(9), 100254.
J Wang, J Pan, F Luan, H Shi, Y Xie, C Zhao, J Zou, Y Shi, D Guo, J Sun and X Zhang. From molecular chaos to precision medicine in the treatment of cardiac hypertrophy: A rational use of natural products by integrating artificial intelligence and multi-omics data. Pharmacological Research 2025; 219(1), 107898.
E Perez-Rivera, C Plasencia and U Ros. The multifaceted role of calcium signaling in regulated necrosis. Biomolecules 2025; 15(6), 854.
AP Kutschat, SA Johnsen and FH Hamdan. Store-operated calcium entry: Shaping the transcriptional and epigenetic landscape in pancreatic cancer. Cells 2021; 10(5), 966.
J Xu, E Minobe and M Kameyama. Ca²⁺ Dyshomeostasis links risk factors to neurodegeneration in Parkinson’s disease. Frontiers in Cellular Neuroscience 2022; 16(1), 867385.
L Daverkausen-Fischer and F Pröls. Regulation of calcium homeostasis and flux between the endoplasmic reticulum and the cytosol. Journal of Biological Chemistry 2022; 298(7), 102061.
X Zhou, Z Chen, L Xiao, Y Zhong, Y Liu, J Wu and H Tao. Intracellular calcium homeostasis and its dysregulation underlying epileptic seizures. Seizure 2022; 103(1), 126-136.
F Moccia, AF Pla, D Lim, F Lodola and A Gerbino. Intracellular Ca²⁺ signalling: Unexpected new roles for the usual suspect. Frontiers in Physiology 2023; 14(1), 1210085.
G Santulli, R Nakashima, Q Yuan and AR Marks. Intracellular calcium release channels: an update. The Journal of Physiology 2017; 595(10), 3041-3051.
D D’Angelo and R Rizzuto. The Mitochondrial Calcium Uniporter (MCU): Molecular identity and role in human diseases. Biomolecules 2023; 13(9), 1304.
Z Zayani, A Matinahmadi, A Tavakolpournegari and SH Bidooki. Exploring stressors: Impact on cellular organelles and implications for cellular functions. Stresses 2025; 5(2), 26.
A Girault, A Ahidouch and H Ouadid-Ahidouch. Roles for Ca²⁺ and K⁺ channels in cancer cells exposed to the hypoxic tumour microenvironment. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2020; 1867(4), 118644.
G Bonsignore, S Martinotti and E Ranzato. Wound repair and Ca²⁺ signalling interplay: The role of Ca²⁺ channels in skin. Cells 2024; 13(6), 491.
CF Yang and WC Tsai. Calmodulin: The switch button of calcium signaling. Tzu Chi Medical Journal 2021; 34(1), 15-22.
AL Deluque, H Dimke and RT Alexander. Biology of calcium homeostasis regulation in intestine and kidney. Nephrology Dialysis Transplantation 2025; 40(3), 435-445.
H Xu and H Van Remmen. The SarcoEndoplasmic Reticulum Calcium ATPase (SERCA) pump: A potential target for intervention in aging and skeletal muscle pathologies. Skeletal Muscle 2021; 11(1), 25.
QS Liao, Q Du, J Lou, JY Xu and R Xie. Roles of Na⁺/Ca²⁺ exchanger 1 in digestive system physiology and pathophysiology. World Journal of Gastroenterology 2019; 25(3), 287-299.
S Ghosh, M Dahiya, A Kumar, M Bheri and GK Pandey. Calcium imaging: A technique to monitor calcium dynamics in biological systems. Physiology and Molecular Biology of Plants 2023; 29(12), 1777-1811.
D Pikor, M Hurła, B Słowikowski, O Szymanowicz, J Poszwa, N Banaszek, A Drelichowska, PP Jagodziński, W Kozubski and J Dorszewska. Calcium ions in the physiology and pathology of the central nervous system. International Journal of Molecular Sciences 2024; 25(23), 13133.
A Villalobo, H Ishida, HJ Vogel and MW Berchtold. Calmodulin as a protein linker and a regulator of adaptor/scaffold proteins. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2018; 1865(3), 507-521.
T Masaki and M Shimada. Decoding the phosphatase code: Regulation of cell proliferation by calcineurin. International Journal of Molecular Sciences 2022; 23(3), 1122.
H-Y Pan, AV Ladd, MR Biswal and M Valapala. Role of nuclear factor of activated T cells (NFAT) pathway in regulating autophagy and inflammation in retinal pigment epithelial cells. International Journal of Molecular Sciences 2021; 22(16), 8684.
H Tokumitsu and H Sakagami. Molecular mechanisms underlying Ca²⁺/calmodulin-dependent protein kinase kinase signal transduction. International Journal of Molecular Sciences 2022; 23(19), 11025.
DO Moon. Calcium’s role in orchestrating cancer apoptosis: Mitochondrial-centric perspective. International Journal of Molecular Sciences 2023; 24(10), 8982.
KH Zent and ML Dell’Acqua. Synapse-to-nucleus ERK→CREB transcriptional signaling requires dendrite-to-soma Ca²⁺ propagation mediated by L-type voltage-gated Ca²⁺ channels. Journal of Neuroscience 2025; 45(4), e1216242024.
Y Bai, Z Zhou, B Han, X Xiang, W Huang and H Yao. Revisiting astrocytic calcium signaling in the brain. Fundamental Research 2024; 4(6), 1365-1374.
L Yan, J Wang, X Cai, YC Liou, HM Shen, J Hao, C Huang, G Luo and W He. Macrophage plasticity: Signaling pathways, tissue repair, and regeneration. MedComm 2024; 5(8), e658.
S Bollimuntha, B Pani and BB Singh. Neurological and motor disorders: Neuronal store-operated Ca²⁺ signaling: An overview and its function. Advances in Experimental Medicine and Biology 2017; 993(1), 535-556.
M Fahrner, H Grabmayr and C Romanin. Mechanism of STIM activation. Current Opinion in Physiology 2020; 17(1), 74-79.
J Pacheco, L Dominguez, A Bohórquez-Hernández, A Asanov and L Vaca. A cholesterol-binding domain in STIM1 modulates STIM1-Orai1 physical and functional interactions. Scientific Reports 2016; 6(1), 29634.
PS Yeung, M Yamashita and M Prakriya. Molecular basis of allosteric Orai1 channel activation by STIM1. The Journal of Physiology 2020; 598(9), 1707-1723.
Q Lu, Y Ding, Y Zhang and S Liu. Viral subversion of host cell Ca²⁺ signaling through STIM1-Orai1-mediated SOCE: Mechanisms and implications. Pharmacological Research 2025; 218(1), 107846.
P Mo and S Yang. The store-operated calcium channels in cancer metastasis: From cell migration, invasion to metastatic colonization. Frontiers in Bioscience 2018; 23(7), 1241-1256.
Z Chao, Q Mei, C Yang, J Luo, P Liu, H Peng, X Guo, Z Yin, L Li and Z Wang. Immunological synapse: Structures, molecular mechanisms and therapeutic implications in disease. Signal Transduction and Targeted Therapy 2025; 10(1), 254.
D Matuz-Mares, M González-Andrade, MG Araiza-Villanueva, MM Vilchis-Landeros and H Vázquez-Meza. Mitochondrial calcium: Effects of its imbalance in disease. Antioxidants 2022; 11(5), 801.
C Delierneux, S Kouba, S Shanmughapriya, M Potier-Cartereau, M Trebak and N Hempel. Mitochondrial calcium regulation of redox signaling in cancer. Cells 2020; 9(2), 432.
J Sun, G Gao, S Wang, H Liu and TS Tang. Decoding the influence of mitochondrial Ca²⁺ regulation on neurodegenerative disease progression. Mitochondrial Communications 2025; 3(1), 1-15.
MP Lazaropoulos and JW Elrod. Mitochondria in pathological cardiac remodeling. Current Opinion in Physiology 2022; 25(1), 100489.
P Wang, S Xu, J Xu, Y Xin, Y Lu, H Zhang, B Zhou, H Xu, SS Sheu, R Tian and W Wang. Elevated MCU expression by CaMKIIδB limits pathological cardiac remodeling. Circulation 2022; 145(14), 1067-1083.
F Borbolis, C Ploumi and K Palikaras. Calcium-mediated regulation of mitophagy: Implications in neurodegenerative diseases. npj Metabolic Health and Disease 2025; 3(1), 4.
J Wang, J Jiang, H Hu and L Chen. MCU complex: Exploring emerging targets and mechanisms of mitochondrial physiology and pathology. Journal of Advanced Research 2025; 68(1), 271-298.
LM McAloon, AG Muller, K Nay, EL Lu, B Smeuninx, AR Means, MA Febbraio and JW Scott. CaMKK2: Bridging the gap between Ca²⁺ signaling and energy-sensing. Essays in Biochemistry 2024; 68(3), 309-320.
JS Brzozowski and KA Skelding. The multi-functional calcium/calmodulin stimulated protein kinase (CaMK) family: Emerging targets for anti-cancer therapeutic intervention. Pharmaceuticals 2019; 12(1), 8.
JW Hussey, WB Limpitikul and IE Dick. Calmodulin mutations in human disease. Channels 2023; 17(1), 2165278.
DC Pipilas, CN Johnson, G Webster, J Schlaepfer, F Fellmann, N Sekarski, LM Wren, KV Ogorodnik, DM Chazin, WJ Chazin, L Crotti, ZA Bhuiyan and AL George. Novel calmodulin mutations associated with congenital long QT syndrome affect calcium current in human cardiomyocytes. Heart Rhythm 2016; 13(10), 2012-2019.
B Badone, C Ronchi, MC Kotta, L Sala, A Ghidoni, L Crotti and A Zaza. Calmodulinopathy: Functional effects of CALM mutations and their relationship with clinical phenotypes. Frontiers in Cardiovascular Medicine 2018; 5(1), 176.
R Ren, J Guo, Y Chen, Y Zhang, L Chen and W Xiong. The role of Ca²⁺ /Calcineurin/NFAT signalling pathway in osteoblastogenesis. Cell Proliferation 2021; 54(11), e13122.
XQ Li, YM Zheng, J Reyes-García and YX Wang. Diversity of ryanodine receptor 1-mediated Ca²⁺ signaling in systemic and pulmonary artery smooth muscle cells. Life Sciences 2021; 270(1), 119016.
D Han, Y Lim, S Lee and SI Eyun. Troponin I - a comprehensive review of its function, structure, evolution, and role in muscle diseases. Animal Cells and Systems 2025; 29(1), 446-468.
YS Borovikov, MV Tishkova, SV Avrova, VV Sirenko and OE Karpicheva. The twisting and untwisting of actin and tropomyosin filaments are involved in the molecular mechanisms of muscle contraction, and their disruption can result in muscle disorders. International Journal of Molecular Sciences 2025; 26(14), 6705.
E Ríos. Calcium-induced release of calcium in muscle: 50 years of work and the emerging consensus. The Journal of General Physiology 2018; 150(4), 521-537.
N Kumari, H Gaur and A Bhargava. Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling. Life Sciences 2018; 194(1), 139-149.
TR Kolstad, J van den Brink, N MacQuaide, PK Lunde, M Frisk, JM Aronsen, ES Norden, A Cataliotti, I Sjaastad, OM Sejersted, AG Edwards, GT Lines and WE Louch. Ryanodine receptor dispersion disrupts Ca²⁺ release in failing cardiac myocytes. Elife 2018; 7(1), e39427.
K Rayani, J Seffernick, AY Li, JP Davis, AM Spuches, F Van Petegem, RJ Solaro, S Lindert and GF Tibbits. Binding of calcium and magnesium to human cardiac troponin C. Journal of Biological Chemistry 2021; 296(1), 100350.
A Njegic, C Wilson and EJ Cartwright. Targeting Ca²⁺ handling proteins for the treatment of heart failure and arrhythmias. Frontiers in Physiology 2020; 11(1), 1068.
P Ježek, B Holendová, M Jabůrek, J Tauber, A Dlasková and L Plecitá-Hlavatá. The pancreatic β-Cell: The perfect redox system. Antioxidants 2021; 10(2), 197.
YD Subbamanda and A Bhargava. Intercommunication between voltage-gated calcium channels and estrogen receptor/estrogen signaling: Insights into physiological and pathological conditions. Cells 2022; 11(23), 3850.
M Lin, Q Zhu, J Wang, W Yang, H Fan, J Yi and M Jiang. Molecules involved in acrosomal exocytosis and cortical granule exocytosis. Biotarget 2017; 1(1), 11.
AT Brunger, J Leitz, Q Zhou, UB Choi and Y Lai. Ca²⁺-Triggered Synaptic Vesicle Fusion Initiated by Release of Inhibition. Trends in Cell Biology 2018; 28(8), 631-645.
AJ Trexler and JW Taraska. Regulation of insulin exocytosis by calcium-dependent protein kinase C in beta cells. Cell Calcium 2017; 67(1), 1-10.
MA Magnuson and AB Osipovich AB. Ca²⁺ signaling and metabolic stress-induced pancreatic β-cell failure. Frontiers in Endocrinology 2024; 15(1), 1412411.
PV Dludla, SE Mabhida, K Ziqubu, BB Nkambule, SE Mazibuko-Mbeje, S Hanser, AK Basson, C Pheiffer and AP Kengne. Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress. World Journal of Diabetes 2023; 14(3), 130-146.
F De Nardi, C Lefort, D Bréard, P Richomme, C Legros and NC Guérineau. Monitoring the secretory behavior of the rat adrenal medulla by high-performance liquid chromatography-based catecholamine assay from slice supernatants. Frontiers in Endocrinology 2017; 8(1), 248.
G Zhao, M Jia, S Zhu, H Ren, G Wang, G Xin, M Sun, X Wang, Q Lin, Q Jiang and C Zhang. Mitotic ER-mitochondria contact enhances mitochondrial Ca²⁺ influx to promote cell division. Cell Reports 2024; 43(10), 114794.
D Zhang, F Wang, P Li and Y Gao. Mitochondrial Ca²⁺ Homeostasis: Emerging Roles and Clinical Significance in Cardiac Remodeling. International Journal of Molecular Sciences 2022; 23(6), 3025.
D Nolfi-Donegan, A Braganza and S Shiva. Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement. Redox Biology 2020; 37(1), 101674.
X Xu, Y Pang and X Fan. Mitochondria in oxidative stress, inflammation and aging: From mechanisms to therapeutic advances. Signal Transduction and Targeted Therapy 2025; 10(1), 190.
G Quarato, F Llambi, CS Guy, J Min, M Actis, H Sun, S Narina, SM Pruett-Miller, J Peng, Z Rankovic and DR Green. Ca²⁺-mediated mitochondrial inner membrane permeabilization induces cell death independently of Bax and Bak. Cell Death & Differentiation 2022; 29(7), 1318-1334.
A Diaz-Vegas, P Sanchez-Aguilera, JR Krycer, PE Morales, M Monsalves-Alvarez, M Cifuentes, BA Rothermel and S Lavandero. Is mitochondrial dysfunction a common root of noncommunicable chronic diseases? Endocrine Reviews 2020; 41(3), bnaa005.
J Mondal and JT Huse. Neurotransmitter power plays: The synaptic communication nexus shaping brain cancer. Acta Neuropathologica Communications 2025; 13(1), 85.
C Costas-Ferreira and LRF Faro. Systematic review of calcium channels and intracellular calcium signaling: Relevance to pesticide neurotoxicity. International Journal of Molecular Sciences 2021; 22(24), 13376.
Q Van Dinh, J Liu and P Dutta. Effect of calcium ion on synaptotagmin-like protein during pre-fusion of vesicle for exocytosis in blood-brain barrier. Biochemistry and Biophysics Reports 2020; 24(1), 100845.
AH Bazzari and HR Parri. Neuromodulators and long-term synaptic plasticity in learning and memory: A steered-glutamatergic perspective. Brain Sciences 2019; 9(11), 300.
AG Mohanan, S Gunasekaran, RS Jacob and RV Omkumar. Role of Ca²⁺/calmodulin-dependent protein kinase Type II in mediating function and dysfunction at glutamatergic synapses. Frontiers in Molecular Neuroscience 2022; 15(1), 855752.
A Uryash, V Flores, JA Adams, PD Allen and JR Lopez. Memory and learning deficits are associated with Ca²⁺ dyshomeostasis in normal aging. Frontiers in Aging Neuroscience 2020; 12(1), 224.
S Khan, N Bano, S Ahamad, U John, NJ Dar and SA Bhat. Excitotoxicity, oxytosis/ferroptosis, and neurodegeneration: Emerging insights into mitochondrial mechanisms. Aging and Disease 2024; 16(5), 2504-2543.
LA Koek, TM Sanderson, J Georgiou and GL Collingridge. The role of calcium stores in long-term potentiation and synaptic tagging and capture in mouse hippocampus. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 2024; 379(1906), 20230241.
Y Wang, Y Shi and H Wei. Calcium dysregulation in Alzheimer’s disease: A target for new drug development. Journal of Alzheimer’s Disease & Parkinsonism 2017; 7(5), 374.
Y Lai, FF Gao, RT Ge, R Liu, S Ma and X Liu. Metal ions overloading and cell death. Cell Biology and Toxicology 2024; 40(1), 72.
R Rajmohan and PH Reddy. Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer’s disease Neurons. Journal of Alzheimer’s Disease 2017; 57(4), 975-999.
A Ni and C Ernst. Evidence That substantia nigra pars compacta dopaminergic neurons are selectively vulnerable to oxidative stress because they are highly metabolically active. Frontiers in Cellular Neuroscience 2022; 16(1), 826193.
R Patil, H Wang, M Kazaleh, G Ailawadi and M Salmon. Dysregulation of mitochondrial homeostasis in cardiovascular diseases. Pharmaceuticals 2025; 18(1), 112.
S Ramesh and ASPM Arachchige. Depletion of dopamine in Parkinson’s disease and relevant therapeutic options: A review of the literature. AIMS Neuroscience 2023; 10(3), 200-231.
I Shemarova. The dysfunction of Ca²⁺ channels in hereditary and chronic human heart diseases and experimental animal models. International Journal of Molecular Sciences 2023; 24(21), 15682.
S Kurihara and N Fukuda. Regulation of myocardial contraction as revealed by intracellular Ca²⁺ measurements using aequorin. The Journal of Physiological Sciences 2024; 74(1), 12.
N Kumari, N Pullaguri, SN Rath, A Bajaj, V Sahu and KKR Ealla. Dysregulation of calcium homeostasis in cancer and its role in chemoresistance. Cancer Drug Resistance 2024; 7(1), 11.
HX Xu, SM Cui, YM Zhang and J Ren. Mitochondrial Ca²⁺ regulation in the etiology of heart failure: physiological and pathophysiological implications. Acta Pharmacologica Sinica 2020; 41(10), 1301-9.
Y Du, LJ Demillard and J Ren. Sarcoplasmic reticulum Ca²⁺ dysregulation in the pathophysiology of inherited arrhythmia: An update. Biochemical Pharmacology 2022; 200(1), 115059.
F Xiao, HL Li, JR Wang, HM Wu, YQ Cai, JW Wang, H Che, G Li, ZY Xia, ZB Xie and S Wang. Research progress on programmed cell death of cardiomyocytes in pressure-overload hypertrophic cardiomyopathy. Apoptosis 2025; 30(9-10), 2191-224.
C Kho. Targeting calcium regulators as therapy for heart failure: focus on the sarcoplasmic reticulum Ca-ATPase pump. Frontiers in Cardiovascular Medicine 2023; 10(1), 1185261.
A Alharbi, Y Zhang and J Parrington. Deciphering the Role of Ca²⁺ Signalling in Cancer Metastasis: From the Bench to the Bedside. Cancers 2021; 13(2), 179.
M Calvo-Rodriguez, EK Kharitonova and BJ Bacskai. Therapeutic strategies to target calcium dysregulation in Alzheimer’s disease. Cells 2020; 9(11), 2513.
AS Hammad and K Machaca. Store operated calcium entry in cell migration and cancer metastasis. Cells 2021; 10(5), 1246.
H Du, T Xu, S Yu, S Wu and J Zhang. Mitochondrial metabolism and cancer therapeutic innovation. Signal Transduction and Targeted Therapy 2025; 10(1), 245.
H Sabit, S Abouelnour, BM Hassen, S Magdy, A Yasser, AS Wadan, S Abdel-Ghany, F Radwan, AI Alqosaibi, H Hafiz, OFA Awlya and B Arneth. Anticancer potential of prebiotics: Targeting estrogen receptors and PI3K/AKT/mTOR in breast cancer. Biomedicines 2025; 13(4), 990.
X Liu, C Feng, L Yan, J Cao, X Zhu, M Li and G Zhao. Calcium channels as pharmacological targets for cancer therapy. Clinical and Experimental Medicine 2025; 25(1), 94.
S Gross, P Mallu, H Joshi, B Schultz, C Go and J Soboloff. Ca²⁺ as a therapeutic target in cancer. Advances in Cancer Research 2020; 148(1), 233-317.
AJ Trexler and JW Taraska. Regulation of insulin exocytosis by calcium-dependent protein kinase C in beta cells. Cell Calcium 2017; 67(1), 1-10.
U Galicia-Garcia, A Benito-Vicente, S Jebari, A Larrea-Sebal, H Siddiqi, KB Uribe, H Ostolaza and C Martín. Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences 2020; 21(17), 6275.
C Klec, G Ziomek, M Pichler, R Malli and WF Graier. Calcium signaling in ß-cell physiology and pathology: A revisit. International Journal of Molecular Sciences 2019; 20(24), 6110.
P Iglesias. Muscle in endocrinology: From skeletal muscle hormone regulation to myokine secretion and its implications in endocrine - metabolic diseases. Journal of Clinical Medicine 2025; 14(13), 4490.
T Khan, R Waseem, Z Zehra, A Aiman, P Bhardwaj, J Ansari, MI Hassan and A Islam. Mitochondrial dysfunction: Pathophysiology and mitochondria-targeted drug delivery approaches. Pharmaceutics 2022; 14(12), 2657.
JS Bhatti, GK Bhatti and PH Reddy. Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2017; 1863(5), 1066-1077.
K Shah, S Seeley, C Schulz, J Fisher and SG Rao. Calcium channels in the heart: Disease states and drugs. Cells 2022; 11(6), 943.
NR Tykocki, EM Boerman and WF Jackson. Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles. Comprehensive Physiology 2017; 7(2), 485-581.
AKS Hamad. Caffeine and Arrhythmias: A critical analysis of cardiovascular responses and arrhythmia susceptibility. Journal of the Saudi Heart Association 2024; 36(4), 335-348.
T Godfraind. Calcium channel blockers in cardiovascular pharmacotherapy. Journal of Cardiovascular Pharmacology and Therapeutics 2014; 19(6), 501-515.
KE Jones, SL Hayden, HR Meyer, JL Sandoz, WH Arata, K Dufrene, C Ballaera, YL Torres, P Griffin, AM Kaye, S Shekoohi and AD Kaye. The evolving role of calcium channel blockers in hypertension management: pharmacological and clinical considerations. Current Issues in Molecular Biology 2024; 46(7), 6315-6327.
E Zuccolo, U Laforenza, F Ferulli, G Pellavio, G Scarpellino, M Tanzi, I Turin, P Faris, A Lucariello, M Maestri, DA Kheder, G Guerra, P Pedrazzoli, D Montagna and F Moccia. Stim and orai mediate constitutive Ca²⁺ entry and control endoplasmic reticulum Ca²⁺ refilling in primary cultures of colorectal carcinoma cells. Oncotarget 2018; 9(57), 31098-31119.
T Lu, Y Zhang, Y Su, D Zhou and Q Xu. Role of store-operated Ca²⁺ entry in cardiovascular disease. Cell Communication and Signaling 2022; 20(1), 33.
Q Zhang, C Wang and L He. ORAI Ca²⁺ channels in cancers and therapeutic interventions. Biomolecules 2024; 14(4), 417.
Y Liao, Y Hao, H Chen, Q He, Z Yuan and J Cheng. Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death. Protein & Cell 2015; 6(6), 434-442.
B O’Rourke, D Ashok and T Liu. Mitochondrial Ca²⁺ in heart failure: Not enough or too much? Journal of Molecular and Cellular Cardiology 2021; 151(1), 126-134.
C Li, J Sun, H Ling, Z Qin, X Zhu, X Fu, T Li and X Gan. MCU regulating bone remodeling and osteogenic function through mitochondrial calcium homeostasis and oxidative stress alteration. Free Radical Biology and Medicine 2025; 236(1), 87-97.
A Michelucci, M García-Castañeda, S Boncompagni and RT Dirksen. Role of STIM1/ORAI1-mediated store-operated Ca²⁺ entry in skeletal muscle physiology and disease. Cell Calcium 2018; 76(1), 101-115.
A Hernández-Oliveras and A Zarain-Herzberg. The role of Ca²⁺-signaling in the regulation of epigenetic mechanisms. Cell Calcium 2024; 117(1), 102836.
M Lisek, O Przybyszewski, L Zylinska, F Guo and T Boczek. The role of MEF2 transcription factor family in neuronal survival and degeneration. International Journal of Molecular Sciences 2023; 24(4), 3120.
K Sałaciak, A Koszałka, E Żmudzka and K Pytka. The calcium/calmodulin-dependent kinases II and IV as therapeutic targets in neurodegenerative and neuropsychiatric disorders. International Journal of Molecular Sciences 2021; 22(9), 4307.
C Gregório, SC Soares-Lima, B Alemar, M Recamonde-Mendoza, D Camuzi, PT de Souza-Santos, R Rivero, S Machado, A Osvaldt, P Ashton-Prolla and LFR Pinto. Calcium signaling alterations caused by epigenetic mechanisms in pancreatic cancer: From early markers to prognostic impact. Cancers 2020; 12(7), 1735.
F Bi, C Gao and H Guo. Epigenetic regulation of cardiovascular diseases induced by behavioral and environmental risk factors: Mechanistic, diagnostic, and therapeutic insights. FASEB BioAdvances 2024; 6(11), 477-502.
MJ Kipanyula, WH Kimaro and PFS Etet. The emerging roles of the calcineurin-nuclear factor of activated T-lymphocytes pathway in nervous system functions and diseases. Journal of Aging Research 2016; 2016(1), 5081021.
S Patergnani, A Danese, E Bouhamida, G Aguiari, M Previati, P Pinton and C Giorgi. Various aspects of calcium signaling in the regulation of apoptosis, autophagy, cell proliferation, and cancer. International Journal of Molecular Sciences 2020; 21(21), 8323.
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