ReviewScientific reports2018
p66Shc activation promotes increased oxidative phosphorylation and renders CNS cells more vulnerable to amyloid beta toxicity.
Review in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Neuroprotective Effect of Fresh Gac Fruit Parts Against β-Amyloid-Induced Toxicity and Its Influence on Synaptic Gene Expression in HT-22 Cell Model.Molecules (Basel, Switzerland) · 2025Article
- The Role of p66Shc in Cancer: Molecular Mechanisms and Therapeutic Implications.Journal of cellular and molecular medicine · 2025Review
- p66Shc deletion confers apoptotic resistance to loss of EGFR-ERK signalling in neural stem cells.Cell death & disease · 2025Article
- Oxidative phosphorylation-related genes for prognosis and tumor microenvironment in breast cancer.Translational cancer research · 2025Article
- Predicting depression severity using machine learning models: Insights from mitochondrial peptides and clinical factors.PloS one · 2025Article
- Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.Molecular medicine (Cambridge, Mass.) · 2024Review
- p66Shc signaling and autophagy impact on C2C12 myoblast differentiation during senescence.Cell death & disease · 2024Article
- Transglutaminase 2 in diabetes mellitus: Unraveling its multifaceted role and therapeutic implications for vascular complications.Theranostics · 2024Review
- The p66International journal of molecular sciences · 2023Review
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- Mitochondria and Oxidative Stress as a Link between Alzheimer's Disease and Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Novel Strategies in the Early Detection and Treatment of Endothelial Cell-Specific Mitochondrial Dysfunction in Coronary Artery Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Brain aerobic glycolysis and resilience in Alzheimer disease.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Isoimperatorin therapeutic effect against aluminum induced neurotoxicity in albino mice.Frontiers in pharmacology · 2023Article
- P66Shc (Shc1) Zebrafish Mutant Line as a Platform for Testing Decreased Reactive Oxygen Species in Pathology.Journal of cardiovascular development and disease · 2022Article
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- To the Future: The Role of Exosome-Derived microRNAs as Markers, Mediators, and Therapies for Endothelial Dysfunction in Type 2 Diabetes Mellitus.Journal of diabetes research · 2022Review
- In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver.International journal of molecular sciences · 2021Article
- Mitochondria-associated membranes (MAMs): a potential therapeutic target for treating Alzheimer's disease.Clinical science (London, England : 1979) · 2021Review
- Lack of Contribution of p66shc to Pressure Overload-Induced Right Heart Hypertrophy.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A key pathological feature of Alzheimer's disease (AD) is the accumulation of the neurotoxic amyloid beta (Aβ) peptide within the brains of affected individuals. Previous studies have shown that neuronal cells selected for resistance to Aβ toxicity display a metabolic shift from mitochondrial-dependent oxidative phosphorylation (OXPHOS) to aerobic glycolysis to meet their energy needs. The Src homology/collagen (Shc) adaptor protein p66Shc is a key regulator of mitochondrial function, ROS production and aging. Moreover, increased expression and activation of p66Shc promotes a shift in the cellular metabolic state from aerobic glycolysis to OXPHOS in cancer cells. Here we evaluated the hypothesis that activation of p66Shc in CNS cells promotes both increased OXPHOS and enhanced sensitivity to Aβ toxicity. The effect of altered p66Shc expression on metabolic activity was assessed in rodent HT22 and B12 cell lines of neuronal and glial origin respectively. Overexpression of p66Shc repressed glycolytic enzyme expression and increased both mitochondrial electron transport chain activity and ROS levels in HT22 cells. The opposite effect was observed when endogenous p66Shc expression was knocked down in B12 cells. Moreover, p66Shc activation in both cell lines increased their sensitivity to Aβ toxicity. Our findings indicate that expression and activation of p66Shc renders CNS cells more sensitive to Aβ toxicity by promoting mitochondrial OXPHOS and ROS production while repressing aerobic glycolysis. Thus, p66Shc may represent a potential therapeutically relevant target for the treatment of AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.