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Pharmaceutics
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Perspective Insights into Therapeutic Approaches in Alzheimer’s Disease
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Perspective Insights into Therapeutic Approaches in Alzheimer’s Disease

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Clinical Pharmaceutics".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 4663

Special Issue Editor

Dr. Gabriela Dumitrița Stanciu

E-Mail Website1 Website2
Guest Editor
Advanced Research and Development Center for Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy of Iasi, Iasi, Romania
Interests: neuroscience; Alzheimer’s disease; in vivo studies; drug development; cannabinoid-based pharmaceuticals; repurposing current therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A large body of studies highlight that Alzheimer’s disease (AD) is a brain disorder, multifactorial in nature, involving various biological mechanisms; it is still an important and growing health challenge worldwide. In the last decades, the cholinergic hypothesis has dominated the pathogenesis and pathophysiology, following a series of research focused on improving the cerebral levels of acetylcholine by inhibiting cholinesterase, thus facilitating cholinergic neurotransmission. The cholinergic approaches offer the most viable therapeutic target across fundamental sign domains of AD, but have a modest influence on improving the progression of this condition. Future pharmacotherapies should not be limited to the postulates of the cholinergic hypothesis.

This Special Issue will bring together original research and review articles on therapeutic approaches in AD focused on developing or repurposing drugs with the ability to target multiple disease features such as risk factors, mechanism-based versus non-mechanism-based approaches, symptomatic therapies, and lifestyle changes.

Dr. Gabriela Dumitrita Stanciu
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 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. Pharmaceutics 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

  • Alzheimer’s disease
  • therapeutic strategies
  • repurposing existing therapeutics
  • multi-target-directed ligands
  • preclinical studies

Published Papers (3 papers)

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Research

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12 pages, 2058 KiB  
Article
Inconsistent Effects of Glatiramer Acetate Treatment in the 5xFAD Mouse Model of Alzheimer’s Disease
by Berke Karaahmet, John A. Olschowka and M. Kerry O’Banion
Pharmaceutics 2023, 15(7), 1809; https://doi.org/10.3390/pharmaceutics15071809 - 24 Jun 2023
Viewed by 950
Abstract
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that involves strong inflammatory components. Aberrant and prolonged inflammation in the CNS is thought to contribute to the development of the pathology. The use of single cytokine approaches to curb or leverage inflammatory mechanisms for [...] Read more.
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that involves strong inflammatory components. Aberrant and prolonged inflammation in the CNS is thought to contribute to the development of the pathology. The use of single cytokine approaches to curb or leverage inflammatory mechanisms for disease modifying benefit has often resulted in conflicting data. Furthermore, these treatments were usually delivered locally into the CNS parenchyma, complicating translational efforts. To overcome these hurdles, we tested the use of glatiramer acetate (GA) in reducing amyloid beta (Aβ) plaque pathology in the 5xFAD model of AD. GA immunizations were begun at the ages of 2.5 months, 5.5 months, and 8.5 months, and GA was delivered weekly for 8 weeks. While previous data describe potential benefits of GA immunization in decreasing Aβ levels in murine models of AD, we found modest decreases in Aβ levels if given during the development of pathology but, surprisingly, found increased Aβ levels if GA was administered at later stages. The impact of GA treatment was only significant for female mice. Furthermore, we observed no changes between microglial uptake of plaque, CD11c immunopositivity of microglia, or levels of TMEM119 and P2Ry12 on microglia. Overall, these data warrant exercising caution when aiming to repurpose GA for AD. Full article
(This article belongs to the Special Issue Perspective Insights into Therapeutic Approaches in Alzheimer’s Disease)
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Review

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34 pages, 1314 KiB  
Review
Monoclonal Antibody Therapy in Alzheimer’s Disease
by Monica Neațu, Anca Covaliu, Iulia Ioniță, Ana Jugurt, Eugenia Irene Davidescu and Bogdan Ovidiu Popescu
Pharmaceutics 2024, 16(1), 60; https://doi.org/10.3390/pharmaceutics16010060 - 29 Dec 2023
Cited by 1 | Viewed by 1766
Abstract
Alzheimer’s disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer’s disease remains without a cure, presenting a [...] Read more.
Alzheimer’s disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer’s disease remains without a cure, presenting a significant global healthcare challenge. Recently, there has been an increased focus on antibody-based treatments as a potentially effective method for dealing with Alzheimer’s disease. This paper offers a comprehensive overview of the current status of research on antibody-based molecules as therapies for Alzheimer’s disease. We will briefly mention their mechanisms of action, therapeutic efficacy, and safety profiles while addressing the challenges and limitations encountered during their development. We also highlight some crucial considerations in antibody-based treatment development, including patient selection criteria, dosing regimens, or safety concerns. In conclusion, antibody-based therapies present a hopeful outlook for addressing Alzheimer’s disease. While challenges remain, the accumulating evidence suggests that these therapies may offer substantial promise in ameliorating or preventing the progression of this debilitating condition, thus potentially enhancing the quality of life for the millions of individuals and families affected by Alzheimer’s disease worldwide. Full article
(This article belongs to the Special Issue Perspective Insights into Therapeutic Approaches in Alzheimer’s Disease)
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25 pages, 892 KiB  
Review
Therapeutic Implications of Renin–Angiotensin System Modulators in Alzheimer’s Dementia
by Daniela-Carmen Ababei, Veronica Bild, Ioana Macadan, Alexandru Vasincu, Răzvan-Nicolae Rusu, Mihaela Blaj, Gabriela Dumitrița Stanciu, Radu-Marian Lefter and Walther Bild
Pharmaceutics 2023, 15(9), 2290; https://doi.org/10.3390/pharmaceutics15092290 - 06 Sep 2023
Cited by 2 | Viewed by 1336
Abstract
The Renin–Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer’s dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors [...] Read more.
The Renin–Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer’s dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and β-amyloid (Aβ) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation’s favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aβ metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies. Full article
(This article belongs to the Special Issue Perspective Insights into Therapeutic Approaches in Alzheimer’s Disease)
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