ArticleNeurochemical research2023
Neuroprotective Role of DPP-4 Inhibitor Linagliptin Against Neurodegeneration, Neuronal Insulin Resistance and Neuroinflammation Induced by Intracerebroventricular Streptozotocin in Rat Model of Alzheimer's Disease.
Article in Neurochemical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- From glycemic control to neuroprotection: alogliptin as a repurposed candidate for Huntington's disease.Metabolic brain disease · 2026Review
- Linagliptin, a Selective DPP-4 Inhibitor, Attenuates Ketamine- and Diazepam-Induced Deficits in Passive Avoidance Performance in Mice.Brain sciences · 2026Article
- Kinetin mitigate neurodegenerative damage of Alzheimer induced by beta-amyloid in male rats by antioxidant and antithrombotic effects.Metabolic brain disease · 2026Article
- Targeting the awry Aβ pathway in Alzheimer's disease: hype and hurdles.Inflammopharmacology · 2025Review
- Insulin signaling disruption exacerbates memory impairment and seizure susceptibility in an epilepsy model with Alzheimer's disease-like pathology.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- GDNF overexpression in astrocytes enhances branching and partially preserves hippocampal function in an Alzheimer's rat model.Scientific reports · 2025Article
- Exploring the Anxiolytic Potential of NPY by a Dipeptidyl Peptidase-IV Inhibitor in an Animal Model of PTSD.The international journal of neuropsychopharmacology · 2024Article
- MST1 selective inhibitor Xmu-mp-1 ameliorates neuropathological changes in a rat model of sporadic Alzheimer's Disease by modulating Hippo-Wnt signaling crosstalk.Apoptosis : an international journal on programmed cell death · 2024Article
- Review
- Neuroprotective Action of Selected Natural Drugs Against Neurological Diseases and Mental Disorders: Potential Use Against Radiation Damage.Neurochemical research · 2024Review
- MSC-Derived Extracellular Vesicles Alleviate NLRP3/GSDMD-Mediated Neuroinflammation in Mouse Model of Sporadic Alzheimer's Disease.Molecular neurobiology · 2024Article
- GSK3-Driven Modulation of Inflammation and Tissue Integrity in the Animal Model.International journal of molecular sciences · 2024Review
- Dysregulated mTOR networks in experimental sporadic Alzheimer's disease.Frontiers in cellular neuroscience · 2024Article
- GLP-1 Analogs, SGLT-2, and DPP-4 Inhibitors: A Triad of Hope for Alzheimer's Disease Therapy.Biomedicines · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is an age-related, multifactorial progressive neurodegenerative disorder manifested by cognitive impairment and neuronal death in the brain areas like hippocampus, yet the precise neuropathology of AD is still unclear. Continuous failure of various clinical trial studies demands the utmost need to explore more therapeutic targets against AD. Type 2 Diabetes Mellitus and neuronal insulin resistance due to serine phosphorylation of Insulin Receptor Substrate-1 at 307 exhibits correlation with AD. Dipeptidyl Peptidase-4 inhibitors (DPP-4i) have also indicated therapeutic effects in AD by increasing the level of Glucagon-like peptide-1 in the brain after crossing Blood Brain Barrier. The present study is hypothesized to examine Linagliptin, a DPP-4i in intracerebroventricular streptozotocin induced neurodegeneration, and neuroinflammation and hippocampal insulin resistance in rat model of AD. Following infusion on 1st and 3rd day, animals were treated orally with Linagliptin (0.513 mg/kg, 3 mg/kg, and 5 mg/kg) and donepezil (5 mg/kg) as a standard for 8 weeks. Neurobehavioral, biochemical and histopathological analysis was done at the end of treatment. Dose-dependently Linagliptin significantly reversed behavioral alterations done through locomotor activity (LA) and morris water maze (MWM) test. Moreover, Linagliptin augmented hippocampal GLP-1 and Akt-ser473 level and mitigated soluble Aβ (1-42), IRS-1 (s307), GSK-3β, TNF-α, IL-1β, IL-6, AchE and oxidative/nitrosative stress level. Histopathological analysis also exhibited neuroprotective and anti-amylodogenic effect in Hematoxylin and eosin and Congo red staining respectively. The findings of our study concludes remarkable dose-dependent therapeutic potential of Linagliptin against neuronal insulin resistance via IRS-1 and AD-related complication. Thus, demonstrates unique molecular mechanism that underlie AD.
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