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

Rajagopalan Iyer; Vibhavari Naik; Basanth Kumar Rayani; Dandamudi Radha Rani; Devi Chaitanya BS; Subramanyeshwar Rao Thammineedi

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):

Rajagopalan Iyer¹,

Vibhavari Naik^2,*,

Basanth Kumar Rayani³,

Dandamudi Radha Rani⁴,

Devi Chaitanya BS⁴,

Subramanyeshwar Rao Thammineedi¹

1Department of Surgical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, India. 500034.

2Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, India.

3Department of Oncoanaesthesiology, Pain and Palliative Medicine, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad. 500034.

4Department of Microbiology, Basavatarakam Indo-American Cancer Institute and Research Center, Hyderabad, India. 500034.

Journal of Cellular & Molecular Anesthesia:Vol. 8, issue 3; e149152

Published online:Jan 27, 2023

Article type:Review_ojs_imported

Received:Oct 02, 2022

Accepted:Dec 02, 2022

How to Cite:Iyer R, Naik V, Rayani B K, Rani D R, BS D C, et al. Metabolic Modeling-Based Drug Repurposing in Statin: An Overview of Mechanistic Approaches in the Management of Craniocerebral Trauma.J Cell Mol Anesth.2023;8(3):e149152.

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

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Author(s):

Rajagopalan Iyer:[PubMed][Scholar]
Vibhavari Naik:[PubMed][Scholar]
Basanth Kumar Rayani:[PubMed][Scholar]
Dandamudi Radha Rani:[PubMed][Scholar]
Devi Chaitanya BS:[PubMed][Scholar]
Subramanyeshwar Rao Thammineedi:[PubMed][Scholar]