ArticleEMBO molecular medicine2012
Modification of γ-secretase by nitrosative stress links neuronal ageing to sporadic Alzheimer's disease.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 79 citations in OpenAlex.
- The Bright and Dark Sides of Nitric Oxide in Neurodegenerative Diseases.Journal of personalized medicine · 2026Review
- Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025Review
- Article
- Neuron-Astrocyte Interactions in Aging and Alzheimer's Disease: Dysregulation of Amyloid Precursor Protein.Ageing & longevity · 2025Article
- The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer's Disease Etiopathology.Antioxidants (Basel, Switzerland) · 2024Review
- Specific Binding of Alzheimer's Aβ Peptides to Extracellular Vesicles.International journal of molecular sciences · 2024Article
- Neuronal Nitric Oxide Synthase and Post-Translational Modifications in the Development of Central Nervous System Diseases: Implications and Regulation.Molecules (Basel, Switzerland) · 2023Review
- The Impact of the Cellular Environment and Aging on Modeling Alzheimer's Disease in 3D Cell Culture Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- The Binding of Different Substrate Molecules at the Docking Site and the Active Site of γ-Secretase Can Trigger Toxic Events in Sporadic and Familial Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Protective Effects of Polysaccharides in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
- Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup.Life science alliance · 2021Article
- Review
- Cocaine potentiates an inflammatory response in C6 astroglia-like cells.Biomedical reports · 2021Article
- Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts.Free radical biology & medicine · 2020Article
- Amyloid Beta-Peptide Increases BACE1 Translation through the Phosphorylation of the Eukaryotic Initiation Factor-2Oxidative medicine and cellular longevity · 2020Article
- Prodromal Alzheimer's Disease: Constitutive Upregulation of Neuroglobin Prevents the Initiation of Alzheimer's Pathology.Frontiers in neuroscience · 2020Article
- Impaired Phasic Discharge of Locus Coeruleus Neurons Based on Persistent High Tonic Discharge-A New Hypothesis With Potential Implications for Neurodegenerative Diseases.Frontiers in neurology · 2020Article
- Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity.Aging cell · 2019Article
- The locus coeruleus neurotoxin, DSP4, and/or a high sugar diet induce behavioral and biochemical alterations in wild-type mice consistent with Alzheimers related pathology.Metabolic brain disease · 2018Article
- Dynamic Nature of presenilin1/γ-Secretase: Implication for Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2018Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
Inherited familial Alzheimer's disease (AD) is characterized by small increases in the ratio of Aβ42 versus Aβ40 peptide which is thought to drive the amyloid plaque formation in the brain of these patients. Little is known however whether ageing, the major risk factor for sporadic AD, affects amyloid beta-peptide (Aβ) generation as well. Here we demonstrate that the secretion of Aβ is enhanced in an in vitro model of neuronal ageing, correlating with an increase in γ-secretase complex formation. Moreover we found that peroxynitrite (ONOO(-)), produced by the reaction of superoxide anion with nitric oxide, promoted the nitrotyrosination of presenilin 1 (PS1), the catalytic subunit of γ-secretase. This was associated with an increased association of the two PS1 fragments, PS1-CTF and PS1-NTF, which constitute the active catalytic centre. Furthermore, we found that peroxynitrite shifted the production of Aβ towards Aβ(42) and increased the Aβ(42) /Aβ(40) ratio. Our work identifies nitrosative stress as a potential mechanistic link between ageing and 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.