ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Early sirtuin 2 inhibition prevents age-related cognitive decline in a senescence-accelerated mouse model.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Pooled it
- SIRT1 in Senescence: Mitochondria and Immune Crosstalk.Biology · 2026Review
- Metabolic reprogramming via SIRT2-deficient microglial large extracellular vesicles ameliorates alzheimer's pathology.Journal of neuroinflammation · 2026Article
- SIRT1 Activators as Geroprotective Agents in Brain Aging: Mechanisms and Therapeutic Potential.Neuromolecular medicine · 2026Review
- Long-term atorvastatin improves cognitive function by modulating SIRT2-mediated dynamic transition of NFL lysine 272 crotonylation to ubiquitination in naturally aging rats.Cell death discovery · 2025Article
- Senescence accelerated mouse-prone 8: a model of neuroinflammation and aging with features of sporadic Alzheimer's disease.Stem cells (Dayton, Ohio) · 2025Review
- Causal association of plasminogen activators and their inhibitors with Alzheimer's disease: a Mendelian randomization study.Archives of medical science : AMS · 2025Article
- Neurobiological and therapeutic landmarks of depression associated with Alzheimer's disease dementia.Frontiers in aging neuroscience · 2025Review
- SIRT2 as a potential new therapeutic target for Alzheimer's disease.Neural regeneration research · 2024Review
- Inhibiting SIRT-2 by AK-7 restrains airway inflammation and oxidative damage promoting lung resurgence through NF-kB and MAP kinase signaling pathway.Frontiers in immunology · 2024Article
- Metabolic mechanisms orchestrated by Sirtuin family to modulate inflammatory responses.Frontiers in immunology · 2024Review
- Review
- SIRT2 counteracts primate cardiac aging.Nature aging · 2023Article
- SIRT2 Inhibition Rescues Neurodegenerative Pathology but Increases Systemic Inflammation in a Transgenic Mouse Model of Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Effect of Sirt3 on hippocampal MnSOD activity, mitochondrial function, physiology, and cognition in an aged murine model.Behavioural brain research · 2023Article
- Aging, Plasminogen Activator Inhibitor 1, Brain Cell Senescence, and Alzheimer's Disease.Aging and disease · 2023Article
- Neuronal SIRT3 Deletion Predisposes to Female-Specific Alterations in Cellular Metabolism, Memory, and Network Excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Aging, longevity, and the role of environmental stressors: a focus on wildfire smoke and air quality.Frontiers in toxicology · 2023Review
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Insulin Deficiency Increases Sirt2 Level in Streptozotocin-Treated Alzheimer's Disease-Like Mouse Model: Increased Sirt2 Induces Tau Phosphorylation Through ERK Activation.Molecular neurobiology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The senescence-accelerated mouse prone-8 (SAMP8) model has been considered as a good model for aged-related cognitive decline and Alzheimer's disease (AD). Since epigenetic alterations represent a crucial mechanism during aging, in the present study we tested whether the inhibition of the histone deacetylase sirtuin 2 (SIRT2) could ameliorate the age-dependent cognitive impairments and associated neuropathology shown by SAMP8 mice. To this end, the potent SIRT2-selective inhibitor, 33i (5 mg/kg i.p. 8 weeks) was administered to 5-month-old (early treatment) and 8-month-old (late treatment) SAMP8 and aged matched control, senescence-accelerated mouse resistant-1 (SAMR1) mice. 33i administration to 5-month-old SAMP8 mice improved spatial learning and memory impairments shown by this strain in the Morris water maze. SAMP8 showed hyperphosphorylation of tau protein and decrease levels of SIRT1 in the hippocampus, which were not altered by 33i treatment. However, this treatment upregulated the glutamate receptor subunits GluN2A, GluN2B, and GluA1 in both SAMR1 and SAMP8. Moreover, early SIRT2 inhibition prevented neuroinflammation evidenced by reduced levels of GFAP, IL-1β, Il-6, and Tnf-α, providing a plausible explanation for the improvement of cognitive deficits shown by 33i-treated SAMP8 mice. When 33i was administered to 8-month-old SAMP8 with a severe established pathology, increases in GluN2A, GluN2B, and GluA1 were observed; however, it was not able to reverse the cognitive decline or the neuroinflammation. These results suggest that early SIRT2 inhibition might be beneficial in preventing age-related cognitive deficits, neuroinflammation, and AD progression and could be an emerging candidate for the treatment of other diseases linked to dementia.
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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.