ArticleAging cell2021
Activation of CREB-mediated autophagy by thioperamide ameliorates β-amyloid pathology and cognition in Alzheimer's disease.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- High intensity 40 Hz flicker improves amyloid pathology and cognition with autophagy in 3xTg mice.iScience · 2026Article
- Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Recognition of the CREB-Binding Protein/Mixed Lineage Leukemia Interface by Sulfonyl-γ-AApeptides: Beyond Mimicry of Mixed Lineage Leukemia.Journal of medicinal chemistry · 2025Article
- CaMK2A/CREB pathway activation is associated with enhanced mitophagy and neuronal apoptosis in diabetic retinopathy.Scientific reports · 2025Article
- Pitolisant alleviates brain network dysfunction and cognitive deficits in a mouse model of Alzheimer's disease.Translational psychiatry · 2025Article
- Targeted autophagic clearance of Tau protects against Alzheimer's disease through amelioration of Tau-mediated lysosomal stress.Theranostics · 2025Article
- Exploring the Neuroprotective Effects of Rufinamide in a Streptozotocin-Induced Dementia Model.Cellular and molecular neurobiology · 2024Article
- Dopamine-conjugated extracellular vesicles induce autophagy in Parkinson's disease.Journal of extracellular vesicles · 2024Article
- Chronic Sleep Deprivation Altered the Expression of Memory-Related Genes and Caused Cognitive Memory Dysfunction in Mice.International journal of molecular sciences · 2024Article
- Dysregulation of CREB5 Impairs Decidualization and Maternal-Fetal Interactions by Inhibiting Autophagy in Recurrent Spontaneous Abortion.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer's Disease, Parkinson's Disease, and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Neuroprotective Effects of Ferrostatin and Necrostatin Against Entorhinal Amyloidopathy-Induced Electrophysiological Alterations Mediated by voltage-gated CaNeurochemical research · 2024Article
- Galangin mitigates glucocorticoid-induced osteoporosis by activating autophagy of BMSCs via triggering the PKA/CREB signaling pathway.Acta biochimica et biophysica Sinica · 2023Article
- Anti-inflammatory effects of new human histamine HInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Neuroprotective effect of astragalin via activating PI3K/Akt-mTOR-mediated autophagy on APP/PS1 mice.Cell death discovery · 2023Article
- Jatrophane Diterpenoids fromInternational journal of molecular sciences · 2023Article
- Exploring the memory: existing activity-dependent tools to tag and manipulate engram cells.Frontiers in cellular neuroscience · 2023Review
- The Role of ERK1/2 Pathway in the Pathophysiology of Alzheimer's Disease: An Overview and Update on New Developments.Cellular and molecular neurobiology · 2023Review
- Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics.Translational neurodegeneration · 2022Review
- Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles.Acta pharmaceutica Sinica. B · 2022Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is an age-related neurodegenerative disease, and the imbalance between production and clearance of β-amyloid (Aβ) is involved in its pathogenesis. Autophagy is an intracellular degradation pathway whereby leads to removal of aggregated proteins, up-regulation of which may be a plausible therapeutic strategy for the treatment of AD. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. Our previous study showed that thioperamide, as an antagonist of H3R, enhances autophagy and protects against ischemic injury. However, the effect of thioperamide on autophagic function and Aβ pathology in AD remains unknown. In this study, we found that thioperamide promoted cognitive function, ameliorated neuronal loss, and Aβ pathology in APP/PS1 transgenic (Tg) mice. Interestingly, thioperamide up-regulated autophagic level and lysosomal function both in APP/PS1 Tg mice and in primary neurons under Aβ-induced injury. The neuroprotection by thioperamide against AD was reversed by 3-MA, inhibitor of autophagy, and siRNA of Atg7, key autophagic-related gene. Furthermore, inhibition of activity of CREB, H3R downstream signaling, by H89 reversed the effect of thioperamide on promoted cell viability, activated autophagic flux, and increased autophagic-lysosomal proteins expression, including Atg7, TFEB, and LAMP1, suggesting a CREB-dependent autophagic activation by thioperamide in AD. Taken together, these results suggested that H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB-mediated autophagy and lysosomal pathway, which contributed to Aβ clearance. This study uncovered a novel mechanism involving autophagic regulating behind the therapeutic effect of thioperamide in AD.
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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.