ArticleTranslational neurodegeneration2018
Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome.
Article in Translational neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 99 citations in OpenAlex.
- Repurposing antimicrobial agents for neuroprotection: Mechanisms, clinical potential, and challenges.Neuroprotection (Chichester, England) · 2026Review
- [Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- A Researcher's guide to rodent models of Down syndrome: Recent insights and translational perspectives.STAR protocols · 2026Review
- Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Engineering exosomes for targeted neurodegenerative therapy: innovations in biogenesis, drug loading, and clinical translation.Theranostics · 2026Review
- Proteome Signature of Alzheimer-Like Phenotypes in Frontal Cortices From Young and Old Individuals With Down Syndrome.Molecular neurobiology · 2025Article
- Intranasal delivery of rapamycin via brain-targeting polymeric micelles for Alzheimer's disease treatment.International journal of pharmaceutics · 2025Article
- Experimental modeling of Alzheimer's disease: Translational lessons from cross-taxon analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- The role of mTOR activation in steroid-resistant asthma: insights from particulate matter-induced mouse model and patient studies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.Biomolecules · 2025Review
- The Usnic Acid Analogue 4-FPBUA Enhances the Blood-Brain Barrier Function and Induces Autophagy in Alzheimer's Disease Mouse Models.ACS chemical neuroscience · 2024Article
- mTOR signaling and Alzheimer's disease: What we know and where we are?CNS neuroscience & therapeutics · 2024Review
- Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease.Physiological reviews · 2024Review
- Engineering memory with an extrinsically disordered kinase.Science advances · 2023Article
- Four anti-aging drugs and calorie-restricted diet produce parallel effects in fat, brain, muscle, macrophages, and plasma of young mice.GeroScience · 2023Article
- Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- A Bioengineering Strategy to Control ADAM10 Activity in Living Cells.International journal of molecular sciences · 2023Article
- Oxidative-Stress-Associated Proteostasis Disturbances and Increased DNA Damage in the Hippocampal Granule Cells of the Ts65Dn Model of Down Syndrome.Antioxidants (Basel, Switzerland) · 2022Article
- Presenilin-1 F105C mutation leads to tau accumulation in human neurons via the Akt/mTORC1 signaling pathway.Cell & bioscience · 2022Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDown syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol (InRapa) that maximizes brain delivery and reduce systemic side effects.
methodsTs65Dn mice were administered with InRapa for 12 weeks, starting at 6 months of age demonstrating, at the end of the treatment by radial arms maze and novel object recognition testing, rescued cognition.
resultsThe analysis of mTOR signalling, after InRapa, demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR (reduced to physiological levels), which led, through the rescue of autophagy and insulin signalling, to reduced APP levels, APP processing and APP metabolites production, as well as, to reduced tau hyperphosphorylation. In addition, a reduction of oxidative stress markers was also observed. DISCUSSION: These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition. Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals.
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