ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
ets-2 promotes the activation of a mitochondrial death pathway in Down's syndrome neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Systematic review of human post-mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer's disease.Neuropathology and applied neurobiology · 2022Pooled it
- Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation.American journal of medical genetics. Part A · 2011Trial
- Identifying and targeting abnormal mitochondrial localization associated with psychosis.bioRxiv : the preprint server for biology · 2026Article
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Cancer and Post-Therapy Cardiotoxicity Risk in Adolescents, Young Adults, and Adults With Down Syndrome.Comprehensive Physiology · 2025Article
- SARS-CoV-2 infection of human cortical cells is influenced by the interaction between aneuploidy and biological sex: insights from a Down syndrome in vitro model.Acta neuropathologica · 2025Article
- Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging?Aging and disease · 2025Review
- A dynamic in vitro model of Down syndrome neurogenesis with trisomy 21 gene dosage correction.Science advances · 2024Article
- Lamivudine modulates the expression of neurological impairment-related genes and LINE-1 retrotransposons in brain tissues of a Down syndrome mouse model.Frontiers in aging neuroscience · 2024Article
- Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging.Archives of toxicology · 2023Review
- Overexpression screen of chromosome 21 genes reveals modulators of Sonic hedgehog signaling relevant to Down syndrome.Disease models & mechanisms · 2023Article
- The Impact of Oxidative Stress on Pediatrics Syndromes.Antioxidants (Basel, Switzerland) · 2022Review
- The accumulation of copper in the brain of Down syndrome promotes oxidative stress: possible mechanism underlying cognitive impairment.Journal of clinical biochemistry and nutrition · 2022Article
- Oxidative Stress in Down and Williams-Beuren Syndromes: An Overview.Molecules (Basel, Switzerland) · 2021Review
- Antioxidants in Down Syndrome: From Preclinical Studies to Clinical Trials.Antioxidants (Basel, Switzerland) · 2020Review
- Challenges and Opportunities for Translation of Therapies to Improve Cognition in Down Syndrome.Trends in molecular medicine · 2020Article
- Down syndrome and Alzheimer's disease: common molecular traits beyond the amyloid precursor protein.Aging · 2020Review
- Article
- Mitochondrial dysfunction in down syndrome: molecular mechanisms and therapeutic targets.Molecular medicine (Cambridge, Mass.) · 2018Review
- On the Origin of Superoxide Dismutase: An Evolutionary Perspective of Superoxide-Mediated Redox Signaling.Antioxidants (Basel, Switzerland) · 2017Review
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Down's syndrome (DS) is characterized by mental retardation and development of Alzheimer's disease (AD). Oxidative stress and mitochondrial dysfunction are both related to neurodegeneration in DS. Several genes in chromosome 21 have been linked to neuronal death, including the transcription factor ets-2. Cortical cultures derived from normal and DS fetal brains were used to study the role of ets-2 in DS neuronal degeneration. ets-2 was expressed in normal human cortical neurons (HCNs) and was markedly upregulated by oxidative stress. When overexpressed in normal HCNs, ets-2 induced a stereotyped sequence of apoptotic changes leading to neuronal death. DS HCNs exhibit intracellular oxidative stress and increased apoptosis after the first week in culture (Busciglio and Yankner, 1995). ets-2 levels were increased in DS HCNs, and, between 7 and 14 d in vitro, DS HCNs showed increased bax, cytoplasmic translocation of cytochrome c and apoptosis inducing factor, and active caspases 3 and 7, consistent with activation of an apoptotic mitochondrial death pathway. Degeneration of DS neurons was reduced by dominant-negative ets-2, suggesting that increased ets-2 expression promotes DS neuronal apoptosis. In the human brain, ets-2 expression was found in neurons and astrocytes. Strong ets-2 immunoreactivity was observed in DS/AD and sporadic AD brains associated with degenerative markers such as bax, intracellular Abeta, and hyperphosphorylated tau. Thus, in DS/AD and sporadic AD brains, converging pathological mechanisms leading to chronic oxidative stress and ets-2 upregulation in susceptible neurons may result in increased vulnerability by promoting the activation of a mitochondrial-dependent proapoptotic pathway of cell death.
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