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Cited by 17Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesNeuroinflammation and Neurodegeneration Mechanisms

RETRACTED ARTICLE: Roflumilast Reduces Pathological Symptoms of Sporadic Alzheimer’s Disease in Rats Produced by Intracerebroventricular Streptozotocin by Inhibiting NF-κB/BACE-1 Mediated Aβ Production in the Hippocampus and Activating the cAMP/BDNF Signalling Pathway

Hasan, Noorul, Zameer, Saima, Najmi, Abul Kalam, Parvez, Suhel, Akhtar, Mohd·2022·Neurotoxicity Research
DOI 10.1007/s12640-022-00482-x
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Abstract

Alzheimer's disease (AD) is a neurological disease that gradually causes memory loss and cognitive impairment. The intracellular secondary messenger cyclic nucleotide cAMP helps in memory acquisition and consolidation. In several models of AD, increasing their levels using phosphodiesterase (PDE) inhibitors improved cognitive performance and prevent memory loss. Thus, the current investigation was undertaken to investigate the therapeutic potential of the PDE-4 inhibitor roflumilast (RFM) against intracerebroventricular (ICV) streptozotocin (STZ)-induced sporadic AD in rats. STZ (3 mg/kg) was given to rats via the ICV route on the stereotaxic apparatus, followed by RFM (0.51 mg/kg/oral) treatment for 15 days, and donepezil (5 mg/kg/oral) was employed as a reference standard drug. Subsequently, we observed that RFM dramatically increased rats learning and memory capacities as measured by the Morris water maze and a novel object recognition task. RFM enhanced the levels of cAMP and brain-derived neurotrophic factors (BDNFs) while decreasing the expression of nuclear factor kappa B (NF-κB) and glial fibrillary acidic protein (GFAP) in the hippocampus of ICV-STZ-infused rats. RFM was found to significantly reduce ICV-STZ-induced neuroinflammation, amyloidogenesis, oxidative stress cholinergic impairments, GSK-3β, and phosphorylated tau levels in the rat hippocampus. Supporting these, histopathological study using Cresyl violet and Congo red demonstrated that RFM reduced neuronal alterations and Aβ deposition in the hippocampus of AD rats. These findings suggest that RFM could be a promising candidate for the management of AD by inhibiting NF-κB/BACE-1 mediated Aβ production in the hippocampus and activating the cAMP/BDNF signalling pathway.

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75 of 75 references verified0 citation errors · 0 not checkable

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  • PDE4 inhibitors include roflumilast, an oral small compound that selectively inhibits PDE4, an enzyme involved in controlling cAMP levels, and may lessen inflammation and increase neuronal survival.

    “PDE4 inhibitors, which are oral small compounds that selectively inhibit PDE4, an enzyme involved in controlling cAMP levels, include roflumilast (15, Figure 5), which may lessen inflammation and increase neuronal survival [177,178,179,180].”

    From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [180]

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Authors
Hasan, N., Zameer, S., Najmi, A. K., Parvez, S., & Akhtar, M.
Affiliations
Jamia Hamdard (IN)
Corresponding author
Akhtar, Mohd
ORCID
Venue
Neurotoxicity Research
Publisher
Springer Science and Business Media LLC
Published
2022-02-22
Volume
40
Issue
2
Pages
432-448
ISSN
  • 1029-8428 (ISSN-L)
  • 1476-3524
DOI
10.1007/s12640-022-00482-x
OpenAlex
W4212976432
Cited by
17
References
75
Citations by year
2026: 1 · 2025: 3 · 2024: 8 · 2023: 4 · 2022: 1
FWCI
2.47
Type
journal article
Language
en
Status
Retracted
Update notices
retraction (2024-07-15)
Open access
closed
Licence
Locations
  • Neurotoxicity Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
roflumilast, sporadic Alzheimer's disease, streptozotocin-induced neurotoxicity, phosphodiesterase-4 inhibitors, amyloid-beta production, hippocampus, neuroinflammation, oxidative stress, tau phosphorylation, GSK3β, learning and memory, retracted article
MeSH terms
Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Aminopyridines, Animals, Benzamides, Cyclopropanes, Disease Models, Animal, Hippocampus, Memory Disorders, Streptozocin, NF-kappa B, Maze Learning, Brain-Derived Neurotrophic Factor, Rats

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