ArticleAging cell2020
RTN4B-mediated suppression of Sirtuin 2 activity ameliorates β-amyloid pathology and cognitive impairment in Alzheimer's disease mouse model.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- Integrated multi-omics analysis identifies potential therapeutic targets for Alzheimer's disease.Neural regeneration research · 2026Article
- Metabolic reprogramming via SIRT2-deficient microglial large extracellular vesicles ameliorates alzheimer's pathology.Journal of neuroinflammation · 2026Article
- STUB1 stabilizes sirtuin 6 via K63-linked ubiquitination to promote NRF2 deacetylation for enhanced ferroptosis resistance after spinal cord injury.Burns & trauma · 2026Article
- APOE4 triggers dysregulated synaptic vesicle release by disrupting SNARE complex assembly.Cellular and molecular life sciences : CMLS · 2025Article
- The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease.Autophagy · 2025Article
- SP3-Mediated Transcriptional Activation of GRIK1 is Involved in Alzheimer's Disease-Induced Cognitive Decline by Inducing Inflammasome Activation in Microglia.Neuromolecular medicine · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Recent advances in potential enzymes and their therapeutic inhibitors for the treatment of Alzheimer's disease.Heliyon · 2024Review
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- Role of SIRT1 in Potentially Toxic Trace Elements (Lead, Fluoride, Aluminum and Cadmium) Associated Neurodevelopmental Toxicity.Biological trace element research · 2024Review
- BubR1 and SIRT2: Insights into aneuploidy, aging, and cancer.Seminars in cancer biology · 2024Review
- Recent Advances in the Discovery of SIRT1/2 Inhibitors via Computational Methods: A Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Oligodendrocyte-derived exosomes-containing SIRT2 ameliorates depressive-like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK-3β pathway in depressed mice.CNS neuroscience & therapeutics · 2024Article
- SIRT2 as a potential new therapeutic target for Alzheimer's disease.Neural regeneration research · 2024Review
- Review
- Cooperative effects of SIRT1 and SIRT2 on APP acetylation.Aging cell · 2023Article
- Novel Thiazole-Based SIRT2 Inhibitors Discovered via Molecular Modelling Studies and Enzymatic Assays.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Label-free quantitative proteomic analyses of mouse astrocytes provides insight into the host response mechanism at different developmental stages of Toxoplasma gondii.PLoS neglected tropical diseases · 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
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirtuin 2 (SIRT2) is an NAD+ dependent deacetylase that is the most abundant sirtuin protein in the brain. Accumulating evidence revealed the role of SIRT2 in a wide range of biological processes and age-related diseases. However, the pivotal mechanism of SIRT2 played in Alzheimer's disease (AD) remains unknown. Here, we report that pharmacological inactivation of SIRT2 has a beneficial effect in AD. The deacetylase inhibitor of SIRT2 rescued the cognitive impairment in amyloid precursor protein/presenilin 1 transgenic mouse (APP/PS1 mouse), and the BACE1 cleavage was weakened to reduce the β-amyloid (Aβ) production in the hippocampus. Moreover, we firstly identified that Reticulon 4B (RTN4B) played a crucial role between SIRT2/BACE1 regulation in AD. RTN4B, as a deacetylation substrate for SIRT2, the deacetylation by SIRT2 drived the ubiquitination and degradation of RTN4B and then the disturbed RTN4B interacted with and influenced the expression of BACE1. When we overexpressed RTN4B in neurons of the hippocampus in the AD mouse model, the abnormal Aβ accumulation and cognitive impairment were ameliorated, consistent with the results of SIRT2 inhibition in vivo. Moreover, we showed that the regulatory effect of SIRT2 on BACE1 is dependent on RTN4B. When RTN4B was knocked down, the effects of SIRT2 inhibition on the BACE1 level, Aβ pathology, and AD-liked behaviors were also blocked. Collectively, we provide evidence that SIRT2 may be a potential target for AD; the new found SIRT2/RTN4B/BACE1 pathological pathway is one of the critical mechanisms for the improvement of SIRT2 on AD.
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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.