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The Development of New Drugs for Alzheimer’s Disease

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: closed (31 December 2022) | Viewed by 7958

Special Issue Editor

Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via E. Orabona 4, 70125 Bari, Italy
Interests: drug design; QSAR; molecular docking; virtual screening; homology modelling; molecular dynamics; GPCRs; metabolic diseases
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Special Issue Information

Dear Colleagues,

According to the latest WHO data, life expectancy is now more than 80 years on average in North American and European countries, and it is increasing (although at a slower pace) in the rest of the world. However, it might be argued that a longer life does not straightforwardly mean living in a better way. At present, welfare state, lifestyle and habits are at high levels, but quality of life is profoundly affected by naturally occurring and almost inescapable biological events (e.g., the degeneration of biological process and the essential functions of the human body). With the advancing age of the population, Alzheimer’s disease is one of the more frequent pathologies to emerge.

The main drugs known so far are cholinesterase inhibitors (donepezil, galantamine and rivastigmine), NMDA antagonists (memantine) and the recent FDA-approved amyloid-b-directed antibody (aducanumab), but there is a strong struggling search for novel chemical principles as alternatives to these molecular entities.

This Special Issue aims to be a compendium focusing on alternative drug design hypotheses based on multifactorial approaches and protocols facing Alzheimer’s disease and neurodegenerative disorders, presenting original manuscripts and short communications in this field.

Prof. Dr. Antonio Carrieri
Guest Editor

Manuscript Submission Information

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Keywords

  • Alzheimer’s disease
  • neurodegenerative diseases
  • multifactorial diseases
  • innovative targets
  • enzyme inhibition
  • drug

Published Papers (3 papers)

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Review

15 pages, 465 KiB  
Review
A Call for Drug Therapies for the Treatment of Social Behavior Disorders in Dementia: Systematic Review of Evidence and State of the Art
by Chiara Cerami, Giulia Perini, Andrea Panzavolta, Matteo Cotta Ramusino and Alfredo Costa
Int. J. Mol. Sci. 2022, 23(19), 11550; https://doi.org/10.3390/ijms231911550 - 30 Sep 2022
Cited by 2 | Viewed by 1576
Abstract
Growing evidence supports the presence of social cognition deficits and social behavior alterations in major and minor neurocognitive disorders (NCDs). Even though the ability to identify socio-emotional changes has significantly improved in recent years, there is still no specific treatment available. Thus, we [...] Read more.
Growing evidence supports the presence of social cognition deficits and social behavior alterations in major and minor neurocognitive disorders (NCDs). Even though the ability to identify socio-emotional changes has significantly improved in recent years, there is still no specific treatment available. Thus, we explored evidence of drug therapies targeting social cognition alterations in NCDs. Papers were selected according to PRISMA guidelines by searching on the PubMed and Scopus databases. Only papers reporting information on pharmacological interventions for the treatment of social cognition and/or social behavioral changes in major and/or minor NCDs were included. Among the 171 articles entered in the paper selection, only 9 papers were eligible for the scope of the review. Trials testing pharmacological treatments for socio-emotional alterations in NCDs are poor and of low-medium quality. A few attempts with neuroprotective, psychoactive, or immunomodulating drugs have been made. Oxytocin is the only drug specifically targeting the social brain that has been tested with promising results in frontotemporal dementia. Its beneficial effects in long-term use have yet to be evaluated. No recommendation can currently be provided. There is a long way to go to identify and test effective targets to treat social cognition changes in NCDs for the ultimate benefit of patients and caregivers. Full article
(This article belongs to the Special Issue The Development of New Drugs for Alzheimer’s Disease)
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24 pages, 6020 KiB  
Review
Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?
by Kinga Czarnota-Łydka, Katarzyna Kucwaj-Brysz, Patryk Pyka, Wawrzyniec Haberek, Sabina Podlewska and Jadwiga Handzlik
Int. J. Mol. Sci. 2022, 23(15), 8768; https://doi.org/10.3390/ijms23158768 - 07 Aug 2022
Cited by 3 | Viewed by 2274
Abstract
In view of the unsatisfactory treatment of cognitive disorders, in particular Alzheimer’s disease (AD), the aim of this review was to perform a computer-aided analysis of the state of the art that will help in the search for innovative polypharmacology-based therapeutic approaches to [...] Read more.
In view of the unsatisfactory treatment of cognitive disorders, in particular Alzheimer’s disease (AD), the aim of this review was to perform a computer-aided analysis of the state of the art that will help in the search for innovative polypharmacology-based therapeutic approaches to fight against AD. Apart from 20-year unrenewed cholinesterase- or NMDA-based AD therapy, the hope of effectively treating Alzheimer’s disease has been placed on serotonin 5-HT6 receptor (5-HT6R), due to its proven, both for agonists and antagonists, beneficial procognitive effects in animal models; however, research into this treatment has so far not been successfully translated to human patients. Recent lines of evidence strongly emphasize the role of kinases, in particular microtubule affinity-regulating kinase 4 (MARK4), Rho-associated coiled-coil-containing protein kinase I/II (ROCKI/II) and cyclin-dependent kinase 5 (CDK5) in the etiology of AD, pointing to the therapeutic potential of their inhibitors not only against the symptoms, but also the causes of this disease. Thus, finding a drug that acts simultaneously on both 5-HT6R and one of those kinases will provide a potential breakthrough in AD treatment. The pharmacophore- and docking-based comprehensive literature analysis performed herein serves to answer the question of whether the design of these kind of dual agents is possible, and the conclusions turned out to be highly promising. Full article
(This article belongs to the Special Issue The Development of New Drugs for Alzheimer’s Disease)
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40 pages, 33810 KiB  
Review
Structural Modifications on Chalcone Framework for Developing New Class of Cholinesterase Inhibitors
by Ginson George, Vishal Payyalot Koyiparambath, Sunitha Sukumaran, Aathira Sujathan Nair, Leena K. Pappachan, Abdullah G. Al-Sehemi, Hoon Kim and Bijo Mathew
Int. J. Mol. Sci. 2022, 23(6), 3121; https://doi.org/10.3390/ijms23063121 - 14 Mar 2022
Cited by 9 | Viewed by 3281
Abstract
Due to the multifaceted pharmacological activities of chalcones, these scaffolds have been considered one of the most privileged frameworks in the drug discovery process. Structurally, chalcones are α, β-unsaturated carbonyl functionalities with two aryl or heteroaryl units. Amongst the numerous pharmacological activities explored [...] Read more.
Due to the multifaceted pharmacological activities of chalcones, these scaffolds have been considered one of the most privileged frameworks in the drug discovery process. Structurally, chalcones are α, β-unsaturated carbonyl functionalities with two aryl or heteroaryl units. Amongst the numerous pharmacological activities explored for chalcone derivatives, the development of novel chalcone analogs for the treatment of Alzheimer’s disease (AD) is among the research topics of most interest. Chalcones possess numerous advantages, such as smaller molecular size, opportunities for further structural modification thereby altering the physicochemical properties, cost-effectiveness, and convenient synthetic methodology. The present review highlights the recent evidence of chalcones as a privileged structure in AD drug development processes. Different classes of chalcone-derived analogs are summarized for the easy understanding of the previously reported analogs as well as the importance of certain functionalities in exhibiting cholinesterase inhibition. In this way, this review will shed light on the medicinal chemistry fraternity for the design and development of novel promising chalcone candidates for the treatment of AD. Full article
(This article belongs to the Special Issue The Development of New Drugs for Alzheimer’s Disease)
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