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Advances in Novel Anti-Alzheimer Drugs: Biological Target, Medicinal Chemistry and Formulation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 4475

Special Issue Editors

Dr. Marc Since

E-Mail Website
Guest Editor
UNICAEN, CERMN, Normandie University, 14000 Caen, France
Interests: drug design; biological targets; medicinal chemistry; formulation
Prof. Dr. Aurélie Malzert-Fréon

E-Mail
Guest Editor
UNICAEN, CERMN, Normandie University, 14000 Caen, France
Interests: nanotechnology; nanoparticles; drug design

Special Issue Information

Dear Colleagues,

Alzheimer’s disease is one of the greatest health and social challenges facing our aging societies. The recent advent of immunotherapy targeting the amyloid peptide triggered a renewed interest in all areas of research in this field. Given the side effects of these biotherapies and their moderate activity, significant progress is expected from the use of new or repositioned small molecules. The wide variety of disease hallmarks offers a very broad panel of biological targets that can be used alone or in combination (polytherapy). The pharmacotechnical development of suitable formulations to improve the cerebral bioavailability of these drugs is a major technological challenge. In this context, anti-Alzheimer drug design requires contributions from different disciplines: biology, medicinal chemistry and formulation.

The aim of this Special Issue is to bring together the latest discoveries in the field of anti-Alzheimer drug design, from the discovery/validation of new biological targets to the synthesis and characterization of new molecules of therapeutic interest and the development of formulations capable of delivering active principles to the brain. Particular attention will be paid to translational approaches. The development of new methods in these research areas will also be considered. The submission of original research papers and reviews on this broad and relevant topic is warmly welcomed.

Dr. Marc Since
Prof. Dr. Aurélie Malzert-Fréon
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Alzheimer’s disease
  • drug design
  • amyloid peptide
  • biological targets
  • medicinal chemistry
  • formulation

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Published Papers (3 papers)

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Research

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21 pages, 8414 KiB  
Article
Effect of Low-Frequency, Low-Energy Pulsed Electromagnetic Fields in Neuronal and Microglial Cells Injured with Amyloid-Beta
by Stefania Merighi, Manuela Nigro, Alessia Travagli, Mercedes Fernandez, Fabrizio Vincenzi, Katia Varani, Silvia Pasquini, Pier Andrea Borea, Simona Salati, Ruggero Cadossi and Stefania Gessi
Int. J. Mol. Sci. 2024, 25(23), 12847; https://doi.org/10.3390/ijms252312847 - 29 Nov 2024
Viewed by 1165
Abstract
Alzheimer’s disease (AD) is a neurodegenerative pathology covering about 70% of all cases of dementia. It is associated with neuroinflammation and neuronal cell death, which are involved in disease progression. There is a lack of effective therapies, and halting this process represents a [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative pathology covering about 70% of all cases of dementia. It is associated with neuroinflammation and neuronal cell death, which are involved in disease progression. There is a lack of effective therapies, and halting this process represents a therapeutic challenge. Data in the literature suggest several neuroprotective effects of low-frequency, low-energy pulsed electromagnetic fields (PEMFs) on biological systems, and clinical studies report that PEMF stimulation is safe and well tolerated. The aim of this work is to investigate the effects of PEMF exposure on oxidative stress and cell death in in vitro-injured cellular models of neurons and microglia. SH-SY5Y cells were stimulated by hydrogen peroxide (H2O2) or amyloid-β (Aβ) peptide, and N9 microglial cells were activated with lipopolysaccharide (LPS) or Aβ peptide. Reactive oxygen production, mitochondrial integrity, and cell death modulation were investigated through 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbo-cyanine iodide (JC-1) biochemical assays, fluorescence, and MTS experiments. Cells were exposed to PEMFs producing a pulsed signal with the following parameters: pulse duration of 1.3 ms and frequency of 75 Hz. The outcomes demonstrated that PEMFs defended SH-SY5Y cells against Aβ peptide- or H2O2-induced oxidative stress, mitochondrial damage, and cell death. Furthermore, in microglia activated by LPS or Aβ peptide, they reverted the reduction in mitochondrial potential, oxidative damage, and cell death. Overall, these findings imply that PEMFs influence the redox state of the cells by significantly boosting antioxidant levels in both injured microglia and neuronal in vitro cells mimicking in vitro AD. Full article
(This article belongs to the Special Issue Advances in Novel Anti-Alzheimer Drugs: Biological Target, Medicinal Chemistry and Formulation)
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20 pages, 2649 KiB  
Article
A Biomimetic Multiparametric Assay to Characterise Anti-Amyloid Drugs
by Willy Smeralda, Marc Since, Sophie Corvaisier, Dimitri Fayolle, Julien Cardin, Sylvain Duprey, Jean-Pierre Jourdan, Christophe Cullin and Aurélie Malzert-Freon
Int. J. Mol. Sci. 2023, 24(23), 16982; https://doi.org/10.3390/ijms242316982 - 30 Nov 2023
Viewed by 1166
Abstract
Alzheimer’s disease (AD) is the most widespread form of senile dementia worldwide and represents a leading socioeconomic problem in healthcare. Although it is widely debated, the aggregation of the amyloid β peptide (Aβ) is linked to the onset and progression of this neurodegenerative [...] Read more.
Alzheimer’s disease (AD) is the most widespread form of senile dementia worldwide and represents a leading socioeconomic problem in healthcare. Although it is widely debated, the aggregation of the amyloid β peptide (Aβ) is linked to the onset and progression of this neurodegenerative disease. Molecules capable of interfering with specific steps in the fibrillation process remain of pharmacological interest. To identify such compounds, we have set up a small molecule screening process combining multiple experimental methods (UV and florescence spectrometry, ITC, and ATR-FTIR) to identify and characterise potential modulators of Aβ1-42 fibrillation through the description of the biochemical interactions (molecule–membrane Aβ peptide). Three known modulators, namely bexarotene, Chicago sky blue and indomethacin, have been evaluated through this process, and their modulation mechanism in the presence of a biomembrane has been described. Such a well-adapted physico-chemical approach to drug discovery proves to be an undeniable asset for the rapid characterisation of compounds of therapeutic interest for Alzheimer’s disease. This strategy could be adapted and transposed to search for modulators of other amyloids such as tau protein. Full article
(This article belongs to the Special Issue Advances in Novel Anti-Alzheimer Drugs: Biological Target, Medicinal Chemistry and Formulation)
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Review

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49 pages, 14007 KiB  
Review
Recent Advances in the Search for Effective Anti-Alzheimer’s Drugs
by Martyna Ogos, Dorota Stary and Marek Bajda
Int. J. Mol. Sci. 2025, 26(1), 157; https://doi.org/10.3390/ijms26010157 - 27 Dec 2024
Cited by 1 | Viewed by 1499
Abstract
Alzheimer’s disease, the most common form of dementia, is characterized by the deposition of amyloid plaques and neurofibrillary tangles in the brain, leading to the loss of neurons and a decline in a person’s memory and cognitive function. As a multifactorial disease, Alzheimer’s [...] Read more.
Alzheimer’s disease, the most common form of dementia, is characterized by the deposition of amyloid plaques and neurofibrillary tangles in the brain, leading to the loss of neurons and a decline in a person’s memory and cognitive function. As a multifactorial disease, Alzheimer’s involves multiple pathogenic mechanisms, making its treatment particularly challenging. Current drugs approved for the treatment of Alzheimer’s disease only alleviate symptoms but cannot stop the progression. Moreover, these drugs typically target a single pathogenic mechanism, leaving other contributing factors unaddressed. Recent advancements in drug design have led to the development of multi-target-directed ligands (MTDLs), which have gained popularity for their ability to simultaneously target multiple pathogenic mechanisms. This paper focuses on analyzing the activity, mechanism of action, and binding properties of the anti-Alzheimer’s MTDLs developed between 2020 and 2024. Full article
(This article belongs to the Special Issue Advances in Novel Anti-Alzheimer Drugs: Biological Target, Medicinal Chemistry and Formulation)
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