ArticleAntioxidants (Basel, Switzerland)2023
Intranasal Administration of KYCCSRK Peptide Rescues Brain Insulin Signaling Activation and Reduces Alzheimer's Disease-like Neuropathology in a Mouse Model for Down Syndrome.
Article in Antioxidants (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- A Researcher's guide to rodent models of Down syndrome: Recent insights and translational perspectives.STAR protocols · 2026Review
- Chasing the FoxO in Metabolic Disorders: Novel Considerations for Oxidative Stress, Programmed Cell Death, Wnt, and the Gut Microbiome.Antioxidants (Basel, Switzerland) · 2026Review
- Metabolic breakdown: Linking insulin resistance and mitochondrial dysfunction to neurodegeneration in Alzheimer's disease.Neural regeneration research · 2026Article
- Osteoarthritis and dementia: contrasting disorders driven by mutual pathways of autophagy, mTOR, GLP-1, AMPK, Wnt, and WISP1.Expert review of clinical pharmacology · 2026Review
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Intranasal Drug Delivery in Neuropharmacology: Advances in Brain-Targeted Therapies and Bioethical Challenges.Biomedicines · 2026Review
- Predictive value of biliverdin reductase-A and homeostasis model assessment of insulin resistance on mild cognitive impairment in patients with type 2 diabetes.Journal of diabetes investigation · 2025Article
- Biliverdin Reductase-A integrates insulin signaling with mitochondrial metabolism through phosphorylation of GSK3β.Redox biology · 2024Article
- Aging exacerbates oxidative stress and liver fibrosis in an animal model of Down Syndrome.Aging · 2024Article
- Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome.Cellular and molecular life sciences : CMLS · 2024Article
- Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024Article
- Review
- Cognitive Impairment in Multiple Sclerosis.Bioengineering (Basel, Switzerland) · 2023Review
- Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans.International journal of molecular sciences · 2023Article
- Article
- The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk.Frontiers in immunology · 2023Review
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Authors and funding
13 authors.
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Abstract
Down syndrome (DS) is the most frequent genetic cause of intellectual disability and is strongly associated with Alzheimer's disease (AD). Brain insulin resistance greatly contributes to AD development in the general population and previous studies from our group showed an early accumulation of insulin resistance markers in DS brain, already in childhood, and even before AD onset. Here we tested the effects promoted in Ts2Cje mice by the intranasal administration of the KYCCSRK peptide known to foster insulin signaling activation by directly interacting and activating the insulin receptor (IR) and the AKT protein. Therefore, the KYCCSRK peptide might represent a promising molecule to overcome insulin resistance. Our results show that KYCCSRK rescued insulin signaling activation, increased mitochondrial complexes levels (OXPHOS) and reduced oxidative stress levels in the brain of Ts2Cje mice. Moreover, we uncovered novel characteristics of the KYCCSRK peptide, including its efficacy in reducing DYRK1A (triplicated in DS) and BACE1 protein levels, which resulted in reduced AD-like neuropathology in Ts2Cje mice. Finally, the peptide elicited neuroprotective effects by ameliorating synaptic plasticity mechanisms that are altered in DS due to the imbalance between inhibitory vs. excitatory currents. Overall, our results represent a step forward in searching for new molecules useful to reduce intellectual disability and counteract AD development in DS.
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