ArticleMetabolic brain disease2019
Roflumilast ameliorates cognitive impairment in APP/PS1 mice via cAMP/CREB/BDNF signaling and anti-neuroinflammatory effects.
Article in Metabolic brain disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 65 citations in OpenAlex.
- Repurposing apremilast for alzheimer's disease: multitarget modulation of cAMP‑PI3K/Akt-GSK‑3β and NF‑κB signaling.Metabolic brain disease · 2026Review
- The lung-brain axis in neurodegeneration: inflammatory, immune, and vascular mechanisms with therapeutic implications.Inflammopharmacology · 2026Review
- Roflumilast Elicits Therapeutic and Neuroprotective Effects in 3-Nitropropionic Acid-Induced Huntington's Disease-Like Neurodegeneration in Rats by Mitigating NLRP3 Inflammasome-Mediated Pyroptosis, Ferroptosis, and Glial Activation.Neurochemical research · 2026Article
- Aberrant brain functional network in COPD patients with cognitive impairment: clinical manifestations, mechanisms and therapeutic strategies.Journal of neuroinflammation · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Neuroprotective Effects of Cilomilast and Chlorogenic Acid Against Scopolamine-Induced Memory Deficits via Modulation of the cAMP/PKA-CREB-BDNF Pathway.International journal of molecular sciences · 2025Article
- Connecting dots: Preclinical foundations to clinical realities of PDE4 inhibitors in Alzheimer's disease.Inflammopharmacology · 2025Review
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- Ethyl Acetate Fraction of Chestnut Honey Attenuates Scopolamine-Induced Cognitive Impairment in Mice and Glutamate-Induced Neurotoxicity in HT22 Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson's disease in rats.Inflammopharmacology · 2024Article
- A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats.PloS one · 2024Article
- Article
- Activation of βMolecular psychiatry · 2023Article
- Therapeutic implications of phosphorylation- and dephosphorylation-dependent factors of cAMP-response element-binding protein (CREB) in neurodegeneration.Pharmacological reports : PR · 2023Review
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- Differential effects of two phosphodiesterase 4 inhibitors against lipopolysaccharide-induced neuroinflammation in mice.BMC neuroscience · 2023Article
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
- Network Proximity-based computational pipeline identifies drug candidates for different pathological stages of Alzheimer's disease.Computational and structural biotechnology journal · 2023Article
- Magnolol upregulates CHRM1 to attenuate Amyloid-β-triggered neuronal injury through regulating the cAMP/PKA/CREB pathway.Journal of natural medicines · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphodiesterase type 4 (PDE4) inhibitors can prevent the breakdown of the second messenger cyclic adenosine monophosphate (cAMP) and improve cognitive performances in several animal models of cognition. However, the clinical development of PDE4 inhibitors has been seriously hampered by severe side effects, such as vomiting and nausea. In this study, we investigated the effect and mechanism of roflumilast, an FDA-approved PDE4 inhibitor for treatment of chronic obstructive pulmonary disease (COPD), on learning and memory abilities in the APP/PS1 mouse model of Alzheimer's disease (AD). APP/PS1 transgenic mice received 3 intragastric doses of roflumilast (0.1, 0.2 and 0.4 mg/kg) daily for 3 weeks followed by behavioral tests. Chronic administration of roflumilast significantly improved the learning and memory abilities of APP/PS1 transgenic mice in the novel object recognition task, Morris water maze, and the step-down passive avoidance task. In addition, roflumilast increased the cAMP, phosphorylated cAMP response-element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) levels, and reduced the nuclear translocation of nuclear factor-kappa B (NF-κB) p65, and proinflammatory cytokine (IL-6, TNF-a and IL-1β) levels in the hippocampus of APP/PS1 transgenic mice. In conclusion, these findings suggest that roflumilast can enhance cognitive function in APP/PS1 transgenic mice, which may be related to its stimulation of the cAMP/CREB/BDNF pathway and anti-neuroinflammatory effects.
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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.