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Advancements in Alzheimer’s Disease Treatment: Exploring Novel Approaches and Strategies

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

Deadline for manuscript submissions: 20 November 2025 | Viewed by 3327

Special Issue Editor

Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD) and related neurodegenerative disorders pose a significant challenge to global health, with an increasing burden on patients, caregivers, and healthcare systems. Despite extensive research, effective treatments and preventive measures for these diseases remain elusive. To address this pressing issue, we invite researchers to submit manuscripts that explore innovative approaches and novel treatment strategies for AD and other related neurodegenerative diseases. We particularly encourage bioinformatics studies which are validated via in vitro and in vivo experiments. We also included traditional preclinical and clinical treatment studies with novel compounds.

We seek submissions that focus on cutting-edge bioinformatics-based research to identify potential pharmacological targets and biomarkers for early detection and intervention. Manuscripts may include, but are not limited to, the following topics:

  1. Computational methods for drug discovery in AD and related neurodegenerative diseases, such as Parkinson’s diseases, demyelinating diseases, prion diseases, post-ischemic brain neurodegeneration, Alzheimer’s disease models, and more.
  2. The identification of novel genetic, epigenetic, and proteomic biomarkers for early diagnosis and prognosis.
  3. Systems biology approaches, unraveling the complex pathophysiology of neurodegenerative disorders.
  4. Machine learning and artificial intelligence techniques for analyzing large-scale omics data related to AD and other related neurodegenerative diseases.
  5. Translational bioinformatics studies that bridge the gap between basic research and clinical applications in AD and other related neurodegenerative diseases.

Through uniting diverse perspectives and methodologies, we will catalyze the development of new strategies for preventing, diagnosing, and treating AD and other related neurodegenerative diseases. The integration of bioinformatics-based approaches with traditional research methods will be pivotal in advancing our understanding of these complex disorders, ultimately contributing to AD prevention and progression.

Dr. Sunmin Park
Guest Editor

Manuscript Submission Information

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Keywords

  • Alzheimer’s disease
  • bioinformatics
  • novel compounds
  • in vitro
  • in vivo
  • clinical study
  • Alzheimer’s disease models

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Published Papers (2 papers)

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Research

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18 pages, 1722 KiB  
Article
Zeaxanthin and Lutein Ameliorate Alzheimer’s Disease-like Pathology: Modulation of Insulin Resistance, Neuroinflammation, and Acetylcholinesterase Activity in an Amyloid-β Rat Model
by Da-Sol Kim, Suna Kang, Na-Rang Moon, Bae-Keun Shin and Sunmin Park
Int. J. Mol. Sci. 2024, 25(18), 9828; https://doi.org/10.3390/ijms25189828 - 11 Sep 2024
Viewed by 1460
Abstract
Alzheimer’s disease (AD) is characterized by impaired insulin/insulin-like growth factor-1 signaling in the hippocampus. Zeaxanthin and lutein, known for their antioxidant and anti-inflammatory properties, have been reported to protect against brain damage and cognitive decline. However, their mechanisms related to insulin signaling in [...] Read more.
Alzheimer’s disease (AD) is characterized by impaired insulin/insulin-like growth factor-1 signaling in the hippocampus. Zeaxanthin and lutein, known for their antioxidant and anti-inflammatory properties, have been reported to protect against brain damage and cognitive decline. However, their mechanisms related to insulin signaling in AD remain unclear. This study investigated the efficacy and mechanisms of zeaxanthin, lutein, and resveratrol in modulating an AD-like pathology in an amyloid-β rat model. Rats were administered hippocampal infusions of 3.6 nmol/day amyloid-β (Aβ)(25-35) for 14 days to induce AD-like memory deficits (AD-CON). Normal control rats received Aβ(35-25) (Normal-CON). All rats had a high-fat diet. Daily, AD rats consumed 200 mg/kg body weight of zeaxanthin (AD-ZXT), lutein (AD-LTN), and resveratrol (AD-RVT; positive-control) or resistant dextrin as a placebo (AD-CON) for eight weeks. The AD-CON rats exhibited a higher Aβ deposition, attenuated hippocampal insulin signaling (reduced phosphorylation of protein kinase B [pAkt] and glycogen synthase kinase-3β [pGSK-3β]), increased neuroinflammation, elevated acetylcholinesterase activity, and memory deficits compared to the Normal-CON group. They also showed systemic insulin resistance and high hepatic glucose output. Zeaxanthin and lutein prevented memory impairment more effectively than the positive-control resveratrol by suppressing acetylcholinesterase activity, lipid peroxidation, and pro-inflammatory cytokines (TNF-α, IL-1β). They also potentiated hippocampal insulin signaling and increased brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CTNF) mRNA expression to levels comparable to the Normal-CON rats. Additionally, zeaxanthin and lutein improved glucose disposal, reduced hepatic glucose output, and normalized insulin secretion patterns. In conclusion, zeaxanthin and lutein supplementation at doses equivalent to 1.5–2.0 g daily in humans may have practical implications for preventing or slowing human AD progression by reducing neuroinflammation and maintaining systemic and central glucose homeostasis, showing promise even when compared to the established neuroprotective compound resveratrol. However, further clinical trials are needed to evaluate their efficacy and safety in human populations. Full article
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Review

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12 pages, 1542 KiB  
Review
Role of 11β-Hydroxysteroid Dehydrogenase and Mineralocorticoid Receptor on Alzheimer’s Disease Onset: A Systematic Review
by Mariangela Di Vincenzo, Pamela Pellegrino, Genny Schiappa, Anna Campanati, Valerio Del Vescovo, Silvia Piccirillo, Patrizia Ambrogini, Giorgio Arnaldi and Monia Orciani
Int. J. Mol. Sci. 2025, 26(3), 1357; https://doi.org/10.3390/ijms26031357 - 6 Feb 2025
Cited by 1 | Viewed by 1223
Abstract
The role of 11β-HSD1 in Alzheimer’s disease (AD) has garnered significant attention due to its involvement in glucocorticoid metabolism, neuroinflammation, and cognitive decline. This review explores the current understanding of 11β-HSD1 in AD, examining genetic, preclinical, and clinical research. Genetic studies have identified [...] Read more.
The role of 11β-HSD1 in Alzheimer’s disease (AD) has garnered significant attention due to its involvement in glucocorticoid metabolism, neuroinflammation, and cognitive decline. This review explores the current understanding of 11β-HSD1 in AD, examining genetic, preclinical, and clinical research. Genetic studies have identified 11β-HSD1 polymorphisms that may influence AD risk, although findings remain inconsistent. Mechanistically, 11β-HSD1 promotes neurodegeneration through the dysregulation of glucocorticoid activity, contributing to hippocampal atrophy, amyloid plaque formation, and tau pathology. Preclinical studies have shown that 11β-HSD1 inhibitors offer neuroprotective effects, including enhanced cognitive function, reduced inflammation, and improved mitochondrial activity. However, clinical trials, including those involving ABT-384 and Xanamem, have produced mixed results, with no substantial cognitive improvements despite effective enzyme inhibition. These inconsistencies highlight the complexity of AD and the challenges in translating preclinical findings into clinical outcomes. Moreover, while 11β-HSD1 inhibition holds therapeutic potential, other strategies targeting neuroinflammation, autophagy, and glucocorticoid signaling are also being explored. Ongoing research is focusing on optimizing 11β-HSD1 inhibitors, identifying biomarkers for patient selection, and investigating combination therapies to enhance treatment efficacy. Ultimately, 11β-HSD1’s role in AD presents a promising therapeutic target, but further studies are required to fully understand its potential in managing the disease. Full article
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