ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
Intranasal Lactoferrin Enhances α-Secretase-Dependent Amyloid Precursor Protein Processing via the ERK1/2-CREB and HIF-1α Pathways in an Alzheimer's Disease Mouse Model.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 108 citations in OpenAlex.
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- β-amyloid and β-amyloid precursor protein synthesis and processing: effects of exercise and exercise-related injury.Frontiers in cellular neuroscience · 2026Review
- Does Antenatal Lactoferrin Protect Hippocampal Development in Ovine Fetuses with Growth Restriction?Cells · 2025Article
- Differences in Plasma Lactoferrin Concentrations Between Subjects with Normal Cognitive Function and Mild Cognitive Impairment: An Observational Study.Healthcare (Basel, Switzerland) · 2025Article
- Liposomal Lactoferrin Reduces Brain Neuroinflammation in Rats and Alleviates Jetlag and Improves Sleep Quality After Long-Haul Travel.NeuroSci · 2025Article
- The role of protein phosphorylation modifications mediated by iron metabolism regulatory networks in the pathogenesis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer's Disease: Beneficial or Detrimental?Antioxidants (Basel, Switzerland) · 2024Review
- Lactoferrin Protects Against Rotenone-Induced Toxicity in Dopaminergic SH-SY5Y Cells through the Modulation of Apoptotic-Associated Pathways.Journal of molecular neuroscience : MN · 2024Article
- The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.International journal of molecular sciences · 2024Review
- Non-invasive Biomarkers for Early Detection of Alzheimer's Disease: a New-Age Perspective.Molecular neurobiology · 2024Review
- Tear Biomarkers and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Lactoferrin: from the structure to the functional orchestration of iron homeostasis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- Therapeutic potential of ADAM10 modulation in Alzheimer's disease: a review of the current evidence.Cell communication and signaling : CCS · 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
- Systematic analysis of cuproptosis-related genes in immunological characterization and predictive drugs in Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Lactoferrin alleviates Western diet-induced cognitive impairment through the microbiome-gut-brain axis.Current research in food science · 2023Article
- The role of microbiome-host interactions in the development of Alzheimer´s disease.Frontiers in cellular and infection microbiology · 2023Review
- Nose-to-brain delivery of self-assembled curcumin-lactoferrin nanoparticles: Characterization, neuroprotective effect andFrontiers in bioengineering and biotechnology · 2023Article
- Intranasal neprilysin rapidly eliminates amyloid-beta plaques, but causes plaque compensations: the explanation why the amyloid-beta cascade may fail?Neural regeneration research · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. In addition, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model. We found that hLf promoted the non-amyloidogenic metabolism of amyloid precursor protein (APP) processing through activation of α-secretase a-disintegrin and metalloprotease10 (ADAM10), resulting in enhanced cleavage of the α-COOH-terminal fragment of APP and the corresponding elevation of the NH2-terminal APP product, soluble APP-α (sAPPα), which consequently reduced Aβ generation and improved spatial cognitive learning ability in AD mice. To gain insight into the molecular mechanism by which Lf modulates APP processing, we evaluated the involvement of the critical molecules for APP cleavage and the signaling pathways in N2a cells stably transfected with Swedish mutant human APP (APPsw N2a cells). The results show that the ERK1/2-CREB and HIF-1α signaling pathways were activated by hLf treatment, which is responsible for the expression of induced ADAM10. Additional tests were performed before suggesting the potential use of hLf as an antioxidant and anti-inflammatory. These findings provide new insights into the sources and mechanisms by which hLf inhibits the cognitive decline that occurs in AD via activation of ADAM10 expression in an ERK1/2-CREB and HIF-1α-dependent manner.
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