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REVIEW article

Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1469211
This article is part of the Research Topic Exploring Small Molecule Inhibitors in Cardiovascular and Cerebrovascular Diseases View all 4 articles

Small molecule inhibitors target multiple neuropathological signaling to exert novel neuroprotection in intracranial aneurysms

Provisionally accepted
Acharya Balkrishna Acharya Balkrishna 1Shalini Mishra Shalini Mishra 1Maneesha Rana Maneesha Rana 1Satyendra K. Rajput Satyendra K. Rajput 2Suhrud Pathak Suhrud Pathak 3Keyi Liu Keyi Liu 3Muralikrishnan Dhanasekaran Muralikrishnan Dhanasekaran 3*Vedpriya Arya Vedpriya Arya 1Shalini Singh Shalini Singh 2*
  • 1 Patanjali Herbal Research Department, Patanjali Research Foundation, Haridwar-249405, India
  • 2 Department of Pharmaceutical Sciences, Gurukula Kangri University, Haridwar, India
  • 3 Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL-36849, United States

The final, formatted version of the article will be published soon.

    Intracranial aneurysms (IAs) represent a critical health concern due to their potential to rupture, leading to severe morbidity and mortality. Small molecule inhibitors (SMIs) have emerged as promising therapeutic candidates for managing IA progression and rupture risk. The current landscape of SMIs targets various molecular pathways implicated in IA pathogenesis, including inflammation, endothelial dysfunction, and extracellular matrix (ECM) degradation. Among the prominent therapeutic candidates discussed are statins, recognized for their multifaceted effects, anti-inflammatory properties, and enhancement of endothelial stability, which may mitigate IA progression. Matrix metalloproteinase inhibitors are also highlighted for their role in preserving ECM structural integrity, essential for preventing IA wall weakening and rupture. Furthermore, the review evaluates the efficacy of anti-inflammatory agents such as corticosteroids and cytokine inhibitors in attenuating IA growth driven by inflammatory processes. Our findings highlight the possibility of several pharmaceutical therapies that target matrix remodeling, inflammation, and other underlying processes to manage cerebral aneurysms. By precisely delivering therapeutic chemicals, such as antioxidants, gene therapy vectors, or anti-inflammatory medicines, to the aneurysm site, these SMI technologies treat the underlying pathophysiological causes while sparing healthy brain tissue. This review underscores the potential of SMIs as adjunctive or primary therapies in the comprehensive management of IAs, emphasizing the need for further clinical research to optimize their efficacy and safety in clinical practice.

    Keywords: Intracranial aneurysm (IA), Small molecule inhibitors (SMIs), pathophysiology, Extracellular Matrix, Inflammation

    Received: 23 Jul 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Balkrishna, Mishra, Rana, Rajput, Pathak, Liu, Dhanasekaran, Arya and Singh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Muralikrishnan Dhanasekaran, Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL-36849, United States
    Shalini Singh, Department of Pharmaceutical Sciences, Gurukula Kangri University, Haridwar, India

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.