Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.7
4.3
Journals
Pharmaceuticals
Special Issues
Pharmacotherapy of Neurodegeneration Disorders
share announcement

Pharmacotherapy of Neurodegeneration Disorders

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 12322

Special Issue Editors

Prof. Dr. Magdalena Kondeva-Burdina

E-Mail Website
Guest Editor
Laboratory “Drug metabolism and drug toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, Sofia, Bulgaria
Interests: neuroprotection; neuroinflammation; oxidative stress; antioxidant activity; MAO inhibition; hepatotoxicity; neurotoxicity; biotransformation
Special Issues, Collections and Topics in MDPI journals
Dr. Maya Georgieva

E-Mail Website
Guest Editor
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University-Sofia, Sofia, Bulgaria
Interests: medicinal chemistry; pharmaceutical chemistry; organic synthesis; heterocycles; drug design and discovery; synthesis and structure-activity relationships of biologically active compounds (small molecules); drug metabolism; pharmacokinetics; pharmacodynamics; drug analysis; chromatography
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A significant increase in the ageing of populations worldwide is especially prevalent in recent decades, with age-related rates steadily increasing. The progressive degeneration and/or death of neuronal cells, resulting in the manifestation of motor (ataxia) and mental disorders (dementia), is linked to a number of neurodegenerative diseases, characterized by the loss of neurons in certain areas of the brain. The current therapeutic strategies in neurodegenerative diseases are mainly aimed at influencing various symptoms, where increasing interest is paid to the key role of oxidative stress and inflammatory processes in the pathogenesis of neurodegenerative diseases. In this relationship, the isolation or synthesis of various biologically active molecules with potential anti-inflammatory and antioxidant effects would expand approaches for the therapy of these diseases beyond conventional treatment, which is accompanied by the manifestation of a number of adverse drug reactions. In addition, the search and the design of new chemically available multitarget agents will add to the search for contemporaneous strategies in neurodegenerative tratment.

Prof. Dr. Magdalena Kondeva-Burdina
Prof. Dr. Maya Georgieva
Guest Editors

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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Pharmaceuticals 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 2900 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

  • neurodegeneration
  • inflammation
  • oxidative stress
  • neuroprotection
  • new biologically active molecules
  • heterocycles
  • synthesis
  • in silico drug design
  • pyrrole
  • MW-assisted synthesis
  • pharmaceutical chemistry

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

25 pages, 17165 KiB  
Article
Mechanistic Insights into the Neuroprotective Potential of Aegle marmelos (L.) Correa Fruits against Aβ-Induced Cell Toxicity in Human Neuroblastoma SH-SY5Y Cells
by Mohd Adnan, Arif Jamal Siddiqui, Fevzi Bardakci, Malvi Surti, Riadh Badraoui and Mitesh Patel
Pharmaceuticals 2025, 18(4), 489; https://doi.org/10.3390/ph18040489 - 28 Mar 2025
Viewed by 619
Abstract
Background/Objectives: Amyloid-β (Aβ) plaque accumulation, oxidative stress, and cholinergic dysfunction are hallmarks of Alzheimer’s disease (AD), a neurodegenerative disability that progresses over time, ultimately resulting in the loss of neurons. The side effects and limitations of current synthetic drugs have shifted attention [...] Read more.
Background/Objectives: Amyloid-β (Aβ) plaque accumulation, oxidative stress, and cholinergic dysfunction are hallmarks of Alzheimer’s disease (AD), a neurodegenerative disability that progresses over time, ultimately resulting in the loss of neurons. The side effects and limitations of current synthetic drugs have shifted attention toward natural alternatives. This study investigates the ethanolic extract of Aegle marmelos (L.) Corrêa fruits for their antioxidant, AChE-inhibitory, and anti-amyloidogenic properties, as well as their neuroprotective effects against amyloid beta-peptide (Aβ1–42). Methods: Phytochemical constituents were identified through HR-LCMS analysis and their antioxidant (DPPH, FRAP) and neuroprotective activities (AChE inhibition, ThT binding, MTT assay, ROS reduction, MMP restoration, and AD-related gene expression via qRT-PCR) were assessed using SHSY-5Y neuroblastoma cells. Results: The extract revealed the existence of flavonoids, phenols, and other bioactive substances. In vitro assays demonstrated strong antioxidant and AChE-inhibitory activities, while the ThT binding assay showed protection against amyloid-β aggregation. The extract exhibited no cytotoxicity in SHSY-5Y cells, even at a concentration of 500 μg/mL, whereas Aβ1–42 at 20 μM induced significant cytotoxicity. Co-treatment with Aβ1–42 (10 μM and 20 μM) and the extract improved cell viability (˃50%) and reduced ROS levels. Additionally, the extract restored mitochondrial membrane potential in Aβ1–42 treated cells, highlighting its role in preserving mitochondrial function. Conclusions: These findings suggest that A. marmelos fruits serve as a powerful source of natural antioxidants, AChE inhibitors, and anti-amyloidogenic agents, positioning them as a compelling option for AD treatment. Full article
(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)
►▼ Show Figures

Figure 1

13 pages, 1758 KiB  
Article
The Effect of Water-Soluble Alpinia Galanga Extract on Sleep and the Activation of the GABAAergic/Serotonergic Pathway in Mice
by Kazim Sahin, Ahmet Kayhan Korkusuz, Emre Sahin, Cemal Orhan, Besir Er, Abhijeet Morde, Muralidhara Padigaru and Ertugrul Kilic
Pharmaceuticals 2024, 17(12), 1649; https://doi.org/10.3390/ph17121649 - 8 Dec 2024
Cited by 1 | Viewed by 1794
Abstract
Background/Objectives: With increasing interest in plant-based compounds that can enhance sleep quality without the side effects of caffeine, Alpinia galanga (AG) has emerged as a promising herbal supplement for improving mental alertness. This study assessed the impact of water-soluble AG extract on sleep [...] Read more.
Background/Objectives: With increasing interest in plant-based compounds that can enhance sleep quality without the side effects of caffeine, Alpinia galanga (AG) has emerged as a promising herbal supplement for improving mental alertness. This study assessed the impact of water-soluble AG extract on sleep quality; the activity of GABAergic, glutamatergic, and serotonergic receptors; and concentrations of dopamine and serotonin in the brains of mice. Methods: The study employed two experimental models using BALB/c mice to examine the impact of pentobarbital-induced sleep and caffeine-induced insomnia. In the first model, a set of 20 mice was assigned to four groups to assess the effects of pentobarbital (42 mg/kg) or pentobarbital with AG extract on sleep induction, with observations made 45 min post-administration. In the second model, 20 mice were divided into four groups to evaluate the impact of caffeine (25 mg/kg) alone or caffeine with varying doses of AG extract (61.25 or 205.50 mg/kg administered orally) on brain activity along with additional analyses on receptor proteins and neurotransmitters. Results: A higher dose of AG extract (205.50 mg/kg) significantly increased total deep sleep duration compared to the caffeine group (p < 0.0001). Furthermore, this dose extended sleep latency and suppressed GABAergic and glutamatergic receptor activity compared to the lower AG dose (p < 0.05). Additionally, the 205.50 mg/kg dose elevated serotonin and dopamine levels compared to caffeine (p < 0.0001), suggesting improved sleep quality alongside enhanced wakefulness. Conclusions: Our data indicate that a higher dose of AG extract improved sleep latency and duration by regulating GABAergic and glutamatergic receptors through the GABAergic/serotonergic pathway in mice. Full article
(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)
►▼ Show Figures

Figure 1

24 pages, 3471 KiB  
Article
Novel Pyrrole Derivatives as Multi-Target Agents for the Treatment of Alzheimer’s Disease: Microwave-Assisted Synthesis, In Silico Studies and Biological Evaluation
by Emilio Mateev, Valentin Karatchobanov, Marjano Dedja, Konstantinos Diamantakos, Alexandrina Mateeva, Muhammed Tilahun Muhammed, Ali Irfan, Magdalena Kondeva-Burdina, Iva Valkova, Maya Georgieva and Alexander Zlatkov
Pharmaceuticals 2024, 17(9), 1171; https://doi.org/10.3390/ph17091171 - 4 Sep 2024
Cited by 3 | Viewed by 2086
Abstract
Considering the complex pathogenesis of Alzheimer’s disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding [...] Read more.
Considering the complex pathogenesis of Alzheimer’s disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding hydrazide–hydrazones (vh1-4) were synthesized by applying highly efficient MW-assisted synthetic protocols. The synthetic pathway provided excellent yields and reduced reaction times under microwave conditions compared to conventional heating. The biological assays indicated that most of the novel pyrroles are selective MAO-B inhibitors with IC50 in the nanomolar range (665 nM) and moderate AChE inhibitors. The best dual-acting MAO-B/AChE inhibitor (IC50 hMAOB–0.665 μM; IC50 eeAChE—4.145 μM) was the unsubstituted pyrrole-based hydrazide (vh0). Importantly, none of the novel molecules displayed hMAOA-blocking capacities. The radical-scavenging properties of the compounds were examined using DPPH and ABTS in vitro tests. Notably, the hydrazide vh0 demonstrated the best antioxidant activities. In addition, in silico simulations using molecular docking and MM/GBSA, targeting the AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z), were utilized to obtain active conformations and to optimize the most prominent dual inhibitor (vh0). The ADME and in vitro PAMPA studies demonstrated that vh0 could cross the blood–brain barrier, and it poses good lead-like properties. Moreover, the optimized molecular structures and the frontier molecular orbitals were examined via DFT studies at 6-311G basis set in the ground state. Full article
(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)
►▼ Show Figures

Figure 1

Review

Jump to: Research

29 pages, 1517 KiB  
Review
Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies
by Rahul Mallick, Sanjay Basak, Premanjali Chowdhury, Prasenjit Bhowmik, Ranjit K. Das, Antara Banerjee, Sujay Paul, Surajit Pathak and Asim K. Duttaroy
Pharmaceuticals 2025, 18(1), 104; https://doi.org/10.3390/ph18010104 - 15 Jan 2025
Cited by 3 | Viewed by 2780
Abstract
Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain [...] Read more.
Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain function, and accelerate disease development. Despite progress in understanding these pathways, effective medicines targeting brain inflammation are still limited. Traditional anti-inflammatory and immunomodulatory drugs are effective in peripheral inflammatory illnesses. Still, they face substantial hurdles when applied to the central nervous system (CNS), such as the blood–brain barrier (BBB) and unwanted systemic effects. This review highlights the developing treatment techniques for modifying cytokine-driven neuroinflammation, focusing on advances that selectively target critical cytokines involved in brain pathology. Novel approaches, including cytokine-specific inhibitors, antibody-based therapeutics, gene- and RNA-based interventions, and sophisticated drug delivery systems like nanoparticles, show promise with respect to lowering neuroinflammation with greater specificity and safety. Furthermore, developments in biomarker discoveries and neuroimaging techniques are improving our ability to monitor inflammatory responses, allowing for more accurate and personalized treatment regimens. Preclinical and clinical trial data demonstrate the therapeutic potential of these tailored techniques. However, significant challenges remain, such as improving delivery across the BBB and reducing off-target effects. As research advances, the creation of personalized, cytokine-centered therapeutics has the potential to alter the therapy landscape for brain illnesses, giving patients hope for better results and a higher quality of life. Full article
(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)
►▼ Show Figures

Figure 1

42 pages, 5459 KiB  
Review
Emerging Perspectives on Prime Editor Delivery to the Brain
by Eli BenDavid, Sina Ramezanian, Yaoyao Lu, Joël Rousseau, Avi Schroeder, Marc Lavertu and Jacques P. Tremblay
Pharmaceuticals 2024, 17(6), 763; https://doi.org/10.3390/ph17060763 - 11 Jun 2024
Cited by 1 | Viewed by 4064
Abstract
Prime editing shows potential as a precision genome editing technology, as well as the potential to advance the development of next-generation nanomedicine for addressing neurological disorders. However, turning in prime editors (PEs), which are macromolecular complexes composed of CRISPR/Cas9 nickase fused with a [...] Read more.
Prime editing shows potential as a precision genome editing technology, as well as the potential to advance the development of next-generation nanomedicine for addressing neurological disorders. However, turning in prime editors (PEs), which are macromolecular complexes composed of CRISPR/Cas9 nickase fused with a reverse transcriptase and a prime editing guide RNA (pegRNA), to the brain remains a considerable challenge due to physiological obstacles, including the blood–brain barrier (BBB). This review article offers an up-to-date overview and perspective on the latest technologies and strategies for the precision delivery of PEs to the brain and passage through blood barriers. Furthermore, it delves into the scientific significance and possible therapeutic applications of prime editing in conditions related to neurological diseases. It is targeted at clinicians and clinical researchers working on advancing precision nanomedicine for neuropathologies. Full article
(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop