Metabolic Modeling-Based Drug Repurposing in Statin: An Overview of Mechanistic Approaches in the Management of Craniocerebral Trauma

Yalda Hosseinzadeh Ardakani; Mohammadreza  Rouini; Mohammad  Sharifzadeh; Mojtaba  Mojtahedzadeh; Sanaz  Jamshidfar; kaveh berenjian

Journal of Cellular & Molecular Anesthesia

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Metabolic Modeling-Based Drug Repurposing in Statin: An Overview of Mechanistic Approaches in the Management of Craniocerebral Trauma

Author(s):

Yalda Hosseinzadeh Ardakani^1,*,

Mohammadreza Rouini¹,

Mohammad Sharifzadeh²,

Mojtaba Mojtahedzadeh³,

Sanaz Jamshidfar⁴,

kaveh berenjian¹

1Department of Pharmaceutics, Biopharmaceutics and Pharmacokinetic Division, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

3Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

4Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Journal of Cellular & Molecular Anesthesia:Vol. 8, issue 3; e149151

Published online:Jan 27, 2023

Article type:Review_ojs_imported

Received:Oct 02, 2022

Accepted:Dec 02, 2022

How to Cite:Yalda Hosseinzadeh ArdakaniMohammadreza Rouini Mohammad SharifzadehMojtaba MojtahedzadehSanaz Jamshidfarkaveh berenjianet al.Metabolic Modeling-Based Drug Repurposing in Statin: An Overview of Mechanistic Approaches in the Management of Craniocerebral Trauma.J Cell Mol Anesth.8(3):e149151.

Abstract

Drug repurposing, known as drug repositioning, is considered a method for redeveloping a compound to utilize in a distinctive illness, which is now becoming a progressively critical procedure for industrial researchers and the scholarly community. A large number of repurposed medicines have been discovered by chance in the lab or through the careful monitoring of drug action in the clinic and retrospective analysis of clinical findings. Additionally, statins are broadly used to treat hyperlipidemia and prevent cardiovascular disease although their application as the neuroprotective agents weakening secondary neurological harm is yet limited in traumatic brain injury (TBI). Their other non-cholesterol-mediated (i.e., pleiotropic) mechanisms of action include upregulating endothelial nitric oxide synthase expression, and enhancing neurogenesis and synaptogenesis, as well as anti-apoptotic effects, increased angiogenesis, and various antioxidant and anti-inflammatory mechanisms. Almost all studies have supported the potential role of statins in neuroprotection, and a few have particularly focused on their effects in traumatic brain injury models. The sulfonylurea receptor 1 (SUR1) protein is a regulatory component linked with pore-forming ion channels. Thus, ATP-sensitive potassium (KATP) channels are created, which can be demonstrated in pancreatic islet cells and certain neurons. Further, transient receptor potential melastatin 4 (TRPM4) is the second pore-forming subunit of SUR1. Upregulating SUR1 and opening SUR1-TRPM4 opening have been observed in the different models related to central nervous system (CNS) injuries such as TBI. Sulfonylurea drugs may prevent neuronal degeneration and improve post-TBI cognitive results by inhibiting the SUR1-TRPM4 channel.

Keywords

Repurposed Drug

Mechanistic Approaches

Traumatic Brain Injury

statins

References

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References are in the PDF file of the article.

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