ArticleGenome medicine2021
Identification and drug-induced reversion of molecular signatures of Alzheimer's disease onset and progression in App
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer's Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil.International journal of molecular sciences · 2023Pooled it
- Progress in cell therapies for neonatal conditions: Proceedings of the Third Neonatal Cell Therapies Symposium (2025).Pediatric research · 2026Article
- Current updates on latest basic research of scientific relevance in hypertensive dementia.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Integration of diverse bioactivity data into the Chemical Checker compound universe.Nature protocols · 2025Review
- Perinatal Choline Supplementation Promotes Resilience Against Progression of Alzheimer's Disease-Like Brain Transcriptomic Signatures in AppAging cell · 2025Article
- Prioritizing repurposable drugs for Alzheimer's disease using network-based analysis with concurrent assessment of Long QT syndrome risk.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- GS-DTI: a graph-structure-aware framework leveraging large language models for drug-target interaction prediction.Bioinformatics (Oxford, England) · 2025Article
- Computational drug repurposing: approaches, evaluation of in silico resources and case studies.Nature reviews. Drug discovery · 2025Review
- Prenatal Stress Increases the Risk of the FPR2-related Dysfunction in the Brain's Resolution of Inflammation: A Study on the Humanized APPCurrent neuropharmacology · 2025Article
- Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Critical thinking of Alzheimer's transgenic mouse model: current research and future perspective.Science China. Life sciences · 2023Review
- Virtual Screening-Based Drug Development for the Treatment of Nervous System Diseases.Current neuropharmacology · 2023Review
- Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications.Frontiers in aging neuroscience · 2023Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn spite of many years of research, our understanding of the molecular bases of Alzheimer's disease (AD) is still incomplete, and the medical treatments available mainly target the disease symptoms and are hardly effective. Indeed, the modulation of a single target (e.g., β-secretase) has proven to be insufficient to significantly alter the physiopathology of the disease, and we should therefore move from gene-centric to systemic therapeutic strategies, where AD-related changes are modulated globally.
methodsHere we present the complete characterization of three murine models of AD at different stages of the disease (i.e., onset, progression and advanced). We combined the cognitive assessment of these mice with histological analyses and full transcriptional and protein quantification profiling of the hippocampus. Additionally, we derived specific Aβ-related molecular AD signatures and looked for drugs able to globally revert them.
resultsWe found that AD models show accelerated aging and that factors specifically associated with Aβ pathology are involved. We discovered a few proteins whose abundance increases with AD progression, while the corresponding transcript levels remain stable, and showed that at least two of them (i.e., lfit3 and Syt11) co-localize with Aβ plaques in the brain. Finally, we found two NSAIDs (dexketoprofen and etodolac) and two anti-hypertensives (penbutolol and bendroflumethiazide) that overturn the cognitive impairment in AD mice while reducing Aβ plaques in the hippocampus and partially restoring the physiological levels of AD signature genes to wild-type levels.
conclusionsThe characterization of three AD mouse models at different disease stages provides an unprecedented view of AD pathology and how this differs from physiological aging. Moreover, our computational strategy to chemically revert AD signatures has shown that NSAID and anti-hypertensive drugs may still have an opportunity as anti-AD agents, challenging previous reports.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.