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Repurposing and Innovation: Drug Research in Neuroprotection

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 1257

Special Issue Editor


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Guest Editor
Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of Pharmacy, Medical University of Varna, 84 A Tsar Osvoboditel Blvd., 9002 Varna, Bulgaria
Interests: neuropharmacology; neuroprotection; neurodegenerative diseases; natural-derived substances; natural products; drug repurposing

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases and a range of neurological disorders remain a major challenge facing modern medicine, and there are currently few treatments that can effectively prevent or reverse neuronal damage. Therefore, the search for neuroprotective strategies aimed at preserving neuronal integrity and function in various diseases has become a core topic in translational medicine research.

From a pharmacological perspective, the study of novel molecules has helped explore various mechanisms, including the regulation of excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, protein misfolding, and altered apoptotic pathways. Innovative compounds are often highly specific, targeting specific molecular cascades or receptors that play a role in neuronal survival and synaptic plasticity. However, they often encounter translational barriers related to toxicity, bioavailability, and blood–brain barrier (BBB) permeability. In contrast, drug repurposing utilizes compounds with well-defined pharmacodynamics and pharmacokinetics, including demonstrated CNS penetration and an established safety profile. Examples include antidiabetic drugs with anti-inflammatory and mitochondrial stabilizing properties and antihypertensive drugs with calcium channel-modulatory properties that enhance neuronal resilience.

Therefore, this Special Issue will cover two interrelated aspects of modern pharmacology: the identification and characterization of novel neuroprotective compounds, and the strategic reuse of existing drugs for neuroprotective applications. We will mainly focus on two approaches: the study of innovative substances with inherent neuroprotective properties and the re-evaluation of clinically approved drugs that were originally designed for other uses but were later shown to have neuroprotective properties. On one hand, we will focus on advances in rational drug design and novel molecular entities derived from natural resources. On the other hand, we will emphasize the importance of systematic drug repurposing, using existing data to accelerate the development of therapeutic interventions while addressing barriers to their translation.

For this Special Issue, we welcome submissions including mechanistic studies, preclinical models, clinical observations, and pharmacological analyses. Our goal is to advance the understanding and application of neuroprotection through innovation and strategic repurposing.

Dr. Stela Dragomanova
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neuroprotection
  • drug repurposing
  • natural-derived compounds
  • neurodegenerative diseases
  • pharmacological innovation

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Published Papers (2 papers)

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Research

20 pages, 1827 KB  
Article
Effects of Citicoline-Based Supplementation on Lipid Peroxidation Markers and Sirtuin-1 Expression in Ischemic Stroke
by Todorka Sokrateva, Bogdan Roussev, Daniela V. Vankova, Deyana G. Vankova, Diana Ivanova, Mihael Tsalta-Mladenov, Darina Georgieva, Miglena N. Nikolova, Galya Mihaylova and Milka A. Nashar
Curr. Issues Mol. Biol. 2026, 48(3), 314; https://doi.org/10.3390/cimb48030314 - 15 Mar 2026
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Abstract
Ischemic stroke (IS) is associated with pronounced oxidative stress and lipid peroxidation, which contribute to secondary neuronal damage. This study explored the effects of a six-month intervention with a new formulation containing citicoline, vitamin C, and extracts from green tea and aronia (Cytodeox™) [...] Read more.
Ischemic stroke (IS) is associated with pronounced oxidative stress and lipid peroxidation, which contribute to secondary neuronal damage. This study explored the effects of a six-month intervention with a new formulation containing citicoline, vitamin C, and extracts from green tea and aronia (Cytodeox™) on arachidonic acid (AA) metabolism, lipid peroxidation assessed by total 8-iso-prostaglandin F2α (8-iso-PGF2α), and Sirtuin-1 (SIRT1) expression in healthy controls (n = 43) and patients with IS (n = 53), both with and without comorbidities. AA and 8-iso-PGF2α were quantified in serum using UPLC–MS and ELISA, respectively, and the fold change in SIRT1 expression was assessed in peripheral blood mononuclear cells (PBMCs) by RT-qPCR. In healthy controls, Cytodeox™ significantly lowered AA and 8-iso-PGF2α levels. IS patients showed markedly increased baseline 8-iso-PGF2α, indicating severe oxidative stress. Following supplementation, 8-iso-PGF2α levels increased in patients with comorbidities, particularly diabetes mellitus (DM), whereas an exploratory analysis suggested a decreasing trend in patients without comorbidities. SIRT1 expression was significantly upregulated in IS patients, with the most pronounced increase observed in the DM subgroup, while remaining unchanged in controls. These findings suggest a protective, antioxidant, and membrane stabilising effect of Cytodeox™ under conditions of preserved or moderately impaired redox homeostasis, supporting its potential role as a preventive or early supportive intervention. Full article
(This article belongs to the Special Issue Repurposing and Innovation: Drug Research in Neuroprotection)
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29 pages, 3225 KB  
Article
Neuroprotective Potential of New Monoterpene-Adamatane Conjugates—A Pilot Study
by Stela Dragomanova, Polina Petkova-Kirova, Konstantin Volcho, Jóhannes Reynisson, Valya Grigorova, Diamara Uzunova, Elina Tsvetanova, Almira Georgieva, Albena Alexandrova, Miroslava Stefanova, Borislav Minchev, Jesunifemi Popoola, Nora Chouha, Aldar Munkuev, Konstantin Ponomarev, Evgenyi Suslov, Nariman Salakhutdinov, Reni Kalfin and Lyubka Tancheva
Curr. Issues Mol. Biol. 2026, 48(2), 145; https://doi.org/10.3390/cimb48020145 - 28 Jan 2026
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Abstract
Neurodegenerative diseases, including Alzheimer’s disease, are marked by cholinergic dysfunction, oxidative stress, and reduced neurotrophic support, which drives the quest for multifunctional therapeutic agents. This pilot study presents four novel monoterpene–aminoadamantane conjugates (MACs 1–4) designed to combine the antioxidant and neuromodulatory characteristics of [...] Read more.
Neurodegenerative diseases, including Alzheimer’s disease, are marked by cholinergic dysfunction, oxidative stress, and reduced neurotrophic support, which drives the quest for multifunctional therapeutic agents. This pilot study presents four novel monoterpene–aminoadamantane conjugates (MACs 1–4) designed to combine the antioxidant and neuromodulatory characteristics of monoterpenes with the neuroprotective properties of aminoadamantane derivatives. Their physicochemical characteristics, blood–brain barrier permeability, and binding affinity to human acetylcholinesterase (AChE) were evaluated using molecular docking and in silico descriptor analysis. In vivo, the neuroprotective efficacy of the MACs was investigated in a scopolamine-induced dementia model in rats, employing behavioral tests. Biochemical assays conducted in the hippocampus and prefrontal cortex assessed AChE activity, antioxidant enzyme performance, lipid peroxidation levels, total glutathione content, and BDNF concentrations. The findings indicate that MAC1, MAC3, and MAC4 demonstrate favorable calculated blood–brain barrier permeability, strong predicted affinity for AChE, and significant in vivo alleviation of scopolamine-induced memory deficits, in conjunction with improvement of key markers of oxidative stress and cholinergic function. These results show that the structural hybridization of myrtenal with aminoadamantane frameworks produces promising multifunctional ligands that are relevant for Alzheimer’s-type neurodegeneration. Full article
(This article belongs to the Special Issue Repurposing and Innovation: Drug Research in Neuroprotection)
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