ArticleBiochimica et biophysica acta2014
Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 154 citations in OpenAlex.
- Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Metformin improves mitophagy-related pathways and mitochondrial-lysosomal homeostasis in chromosome 21 trisomic fibroblasts.Cellular and molecular life sciences : CMLS · 2026Article
- Systematic multi-omic deconvolution of the clinical heterogeneity of Down syndrome.Nature communications · 2026Article
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Proteome Signature of Alzheimer-Like Phenotypes in Frontal Cortices From Young and Old Individuals With Down Syndrome.Molecular neurobiology · 2025Article
- Analysis of Specific Serum Markers for Early Prediction of Alzheimer's Disease in Adolescents with Down Syndrome.Indian journal of clinical biochemistry : IJCB · 2025Article
- Oxidative stress biomarkers as novel screening tools for trisomy 21: a case-control study.BMC pregnancy and childbirth · 2025Article
- The apoptotic and anti-proliferative effects of Neosetophomone B in T-cell acute lymphoblastic leukaemia via PI3K/AKT/mTOR pathway inhibition.Cell proliferation · 2025Article
- Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.Biomolecules · 2025Review
- Neuroprotection against beta-amyloid toxicity by the novel estrogen receptor modulator STX requires convergent signaling pathways.Frontiers in molecular neuroscience · 2025Article
- Current insights and prospects for the pathogenesis and treatment of clinical manifestations associated with Down syndrome through neurotransmitter, inflammatory, and oxidative stress pathways.Frontiers in pharmacology · 2025Review
- Review
- The mTOR Pathway: A Common Link Between Alzheimer's Disease and Down Syndrome.Journal of clinical medicine · 2024Review
- Review
- Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer's disease.Nature communications · 2024Article
- Protein restriction slows the development and progression of Alzheimer's disease in mice.Research square · 2024Article
- Autophagy is a promising process for linking inflammation and redox homeostasis in Down syndrome.Frontiers in pharmacology · 2024Review
- Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease.Physiological reviews · 2024Review
- Conquering Insulin Network Dysfunctions in Alzheimer's Disease: Where Are We Today?Journal of Alzheimer's disease : JAD · 2024Review
- Long non‑coding RNAExperimental and therapeutic medicine · 2023Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Down syndrome (DS) is the most frequent genetic cause of intellectual disability characterized by the presence of three copies of chromosome 21 (Chr21). Individuals with DS have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD) after the age of 40years. The aim of our study is to gain new insights in the molecular mechanisms impaired in DS subjects that eventually lead to the development of dementia. We evaluate the PI3K/Akt/mTOR axis in the frontal cortex from DS cases (under the age of 40years) and DS with AD neuropathology compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis may control several key pathways involved in AD that, if aberrantly regulated, affect amyloid beta (Aβ) deposition and tau phosphorylation. Our results show a hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD pathology, in comparison with respective controls. The PI3K/Akt/mTOR deregulation results in decreased autophagy, inhibition of IRS1 and GSK3β activity. Moreover, our data suggest that aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD. In conclusion, this study provides insights into the neuropathological mechanisms that may be engaged during the development of AD in DS. We suggest that deregulation of this signaling cascade is already evident in young DS cases and persist in the presence of AD pathology. The impairment of the PI3K/Akt/mTOR axis in DS population might represent a key-contributing factor to the neurodegenerative process that culminates in Alzheimer-like dementia.
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