Last update 01 Nov 2024

CACNA2D2

Last update 01 Nov 2024

Basic Info

Synonyms

CACNA2D2, calcium channel, voltage-dependent, alpha 2/delta subunit 2, calcium voltage-gated channel auxiliary subunit alpha2delta 2

+ [6]

Introduction

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G) (PubMed:15111129, PubMed:23339110). Overexpression induces apoptosis.

Drugs associated with CACNA2D2

Mirogabalin Besilate

Target

CACNA2D1 x CACNA2D2

Mechanism

CACNA2D1 blockers [+1]

Active Org.

Daiichi Sankyo Co., Ltd. [+1]

Originator Org.

Daiichi Sankyo Co., Ltd.

Active Indication

Diabetic peripheral neuropathic pain [+1]

Inactive Indication

Chronic Kidney Diseases [+2]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date08 Jan 2019

Gabapentin Enacarbil

Target

CACNA2D1 x CACNA2D2

Mechanism

CACNA2D1 blockers [+1]

Active Org.

Azurity Pharmaceuticals, Inc. [+1]

Originator Org.

XenoPort, Inc.

Active Indication

Neuralgia, Postherpetic [+1]

Inactive Indication

Alcohol Use Disorder [+2]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date06 Apr 2011

Pregabalin

Target

CACNA2D1 x CACNA2D2

Mechanism

CACNA2D1 blockers [+1]

Active Org.

Huizhi Pharmaceutical (Dalian) Co., Ltd. [+14]

Originator Org.

The Upjohn Co.

Active Indication

Fibromyalgia [+9]

Inactive Indication

Acute herpes zoster neuropathy [+32]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

EU [+3]

First Approval Date05 Jul 2004

1,706

Clinical Trials associated with CACNA2D2

NCT06614322 / Not yet recruitingPhase 2IIT

Sensory Phenotyping to Enhance Neuropathic Pain Drug Development (SPENDD): a Randomized, Double-blinded Cross-over Clinical Trial Aimed At Investigating Whether Bedside Quantitative Sensory Testing Can Predict Response to Analgesics.

The goal of this clinical trial is to determine whether quantitative sensory testing (QST) can be used to classify participants into pain sub-groups and predict who will respond best to certain pain treatments in participants with painful peripheral neuropathy.
The analgesic effect is evaluated by measuring pain intensity and Patient Global Impression of Change (PGIC).
This study is a 3-period cross-over trial. This means researchers will compare 3 different drugs (pregabalin, duloxetine, and placebo) over a period of 19 weeks.
Participants will:
* Undergo a quantitative sensory testing (QST) exam.
* Provide a blood sample.
* Complete questionnaires on the computer.
* Take the study drug as instructed.

Start Date01 Sep 2025

Sponsor / Collaborator

University of Rochester

[+1]

CTRI/2024/09/074067 / Not yet recruitingPhase 3IIT

Evaluation of efficacy and safety of add-on olanzapine plus pregabalin versus add-on aprepitant to ondansetron in preventing nausea and vomiting in patients undergoing highly emetogenic chemotherapy: A randomized, double-blind, add-on active-controlled, group-sequential and non-inferiority clinical trial - NIL

Start Date01 Nov 2024

Sponsor / Collaborator-

IRCT20190325043107N49 / SuspendedPhase 2/3IIT

Comparison of the effects of gabapentin plus different doses of dexamethasone in the management of acute pain after septoplasty

Start Date20 Oct 2024

Sponsor / Collaborator

Tabriz University of Medical Sciences

100 Clinical Results associated with CACNA2D2

100 Translational Medicine associated with CACNA2D2

0 Patents (Medical) associated with CACNA2D2

152

Literatures (Medical) associated with CACNA2D2

04 Oct 2024·European Heart Journal - Cardiovascular Pharmacotherapy

Utilizing genetics and proteomics to assess the role of antihypertensive drugs in human longevity and the underlying pathways: a Mendelian randomization study

Article

Author: Zhao, Jie V ; Fan, Bohan

AbstractBackgroundAntihypertensive drugs are known to lower cardiovascular mortality, but the role of different types of antihypertensive drugs in lifespan has not been clarified. Moreover, the underlying mechanisms remain unclear.Methods and ResultsTo minimize confounding, we used Mendelian randomization to assess the role of different antihypertensive drug classes in longevity and examined the pathways via proteins. Genetic variants associated with systolic blood pressure (SBP) corresponding to drug-target genes were used as genetic instruments. The genetic associations with lifespan were obtained from a large genome-wide association study including 1 million European participants from UK Biobank and LifeGen. For significant antihypertensive drug classes, we performed sex-specific analysis, drug-target analysis, and colocalization. To examine the mediation pathways, we assessed the associations of 2291 plasma proteins with lifespan, and examined the associations of drug classes with the proteins affecting lifespan. After correcting for multiple testing, genetically proxied beta-blockers (BBs), calcium channel blockers (CCBs), and vasodilators were related to longer life years (BBs: 2.03, 95% CI 0.78–3.28 per 5 mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47–5.33, and vasodilators: 2.92, 95% CI 1.08–4.77). The beneficial effects of BBs and CCBs were more obvious in men. ADRB1, CACNA2D2, CACNB3, CPT1A, CPT2, and EDNRA genes were related to extended lifespan, with CPT2 further supported by colocalization evidence. Eighty-six proteins were related to lifespan, of which four proteins were affected by CCBs. CDH1 may mediate the association between CCBs and lifespan.ConclusionsBeta-blockers, CCBs, and vasodilators may prolong lifespan, with potential sex differences for BBs and CCBs. The role of CCBs in lifespan is partly mediated by CDH1. Prioritizing the potential protein targets can provide new insights into healthy aging.

01 Aug 2024·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

A novel function of claudin-5 in maintaining the structural integrity of the heart and its implications in cardiac pathology

Article

Author: Zhang, Yi ; Zhu, Jiabiao ; Cui, Guozhen ; Luo, Tao ; Kim, Jin Kyung ; Liu, Haiqiong ; Wang, Miao ; Zhang, Yu ; Chen, Baihe ; Kitakaze, Masafumi ; Wu, Yuanzhou ; Wang, Xianbao ; Wang, Yiyang ; Liu, Daishun ; Chen, Minjun

This study aims to investigate the role of claudin-5 (Cldn5) in cardiac structural integrity. Proteomic analysis was performed to screen the protein profiles in enlarged left atrium from atrial fibrillation (AF) patients. Cldn5 shRNA adeno-associated virus (AAV) or siRNA was injected into the mouse left ventricle or added into HL1 cells respectively to knockdown Cldn5 in cardiomyocytes to observe whether the change of Cldn5 influences cardiac morphology and function, and affects those protein expressions stem from the proteomic analysis. Mitochondrial density and membrane potential were also measured by Mitotracker staining and JC-1 staining under the confocal microscope in HL1 cells. Cldn5 was reduced in cardiomyocytes from the left atrial appendage of AF patients compared to non-AF donors. Proteomic analysis showed 83 proteins were less abundant and 102 proteins were more abundant in AF patients. KEGG pathway analysis showed less abundant CACNA2D2, CACNB2, MYL2 and MAP6 were highly associated with dilated cardiomyopathy. Cldn5 shRNA AAV injection caused severe cardiac atrophy, dilation and myocardial dysfunction in mice. The decreases in mitochondrial numbers and mitochondrial membrane potentials in HL1 cells were observed after Cldn5 knockdown. We demonstrated for the first time the mechanism of Cldn5 downregulation-induced myocyte atrophy and myocardial dysfunction might be associated with the downregulation of CACNA2D2, CACNB2, MYL2 and MAP6, and mitochondrial dysfunction in cardiomyocytes.

01 Jul 2024·Journal of Biological Chemistry

Circular RNA circMYLK4 shifts energy metabolism from glycolysis to OXPHOS by binding to the calcium channel auxiliary subunit CACNA2D2

Article

Author: Sun, Xiaohui ; Yang, Jinjin ; Shi, Xine ; Yang, Gongshe ; Li, Xiao ; Cao, Haigang ; Jin, Jianjun ; Li, Chenchen

Skeletal muscle is heterogeneous tissue, composed of fast-twitch fibers primarily relying on glycolysis and slow-twitch fibers primarily relying on oxidative phosphorylation. The relative expression and balance of glycolysis and oxidative phosphorylation in skeletal muscle are crucial for muscle growth and skeletal muscle metabolism. Here, we employed multi-omics approaches including transcriptomics, proteomics, phosphoproteomics, and metabolomics to unravel the role of circMYLK4, a differentially expressed circRNA in fast and slow-twitch muscle fibers, in muscle fiber metabolism. We discovered that circMYLK4 inhibits glycolysis and promotes mitochondrial oxidative phosphorylation. Mechanistically, circMYLK4 interacts with the voltage-gated calcium channel auxiliary subunit CACNA2D2, leading to the inhibition of Ca²⁺ release from the sarcoplasmic reticulum. The decrease in cytoplasmic Ca²⁺ concentration inhibits the expression of key enzymes, PHKB and PHKG1, involved in glycogen breakdown, thereby suppressing glycolysis. On the other hand, the increased fatty acid β-oxidation enhances the tricarboxylic acid cycle and mitochondrial oxidative phosphorylation. In general, circMYLK4 plays an indispensable role in maintaining the metabolic homeostasis of skeletal muscle.

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CACNA2D2

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