ArticleCommunications biology2023
Synaptic proteasome is inhibited in Alzheimer's disease models and associates with memory impairment in mice.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 20 citations in OpenAlex.
- Proteostasis and ageing dissidence.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- Zinc-mediated lysosomal activation by 1H10 enhances autophagy and attenuates tau pathology in Alzheimer's disease models.Molecular brain · 2026Article
- Composition and activity of the proteasome in human iPSC-derived neuronal model of early-stage sporadic Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Irisin promotes selective changes in hippocampal mitochondrial metabolism in mice.Biochemistry and biophysics reports · 2026Article
- Translational Insights into Exercise-Induced Protective Adaptations in 5XFAD Mice and Middle-Aged Amateur Sportsmen.Antioxidants (Basel, Switzerland) · 2026Article
- FBXW7α regulates amyloid pathology by mediating ubiquitination and degradation of BACE1 in Alzheimer's disease.Cell death discovery · 2026Article
- α/Sulfonyl-γ-AApeptide foldamers mitigate Alzheimer's disease pathology by stabilizing transient helical domains in Aβ.Nature communications · 2026Article
- Unveiling ribosomal dysfunction and impaired signaling pathways in the cortical region of 5xFAD mice.Acta neuropathologica communications · 2026Article
- Article
- Deep Proteome Profiling of Rat Dorsal Striatal Synaptoneurosomes Following Methamphetamine Exposure.ACS chemical neuroscience · 2026Article
- The emerging role of ubiquitin-proteasome system dysfunction in the pathogenesis of perioperative neurocognitive disorders: a narrative review.Frontiers in behavioral neuroscience · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Early proteasome downregulation and dysfunction drive proteostasis failure in Alzheimer's disease.Brain : a journal of neurology · 2025Article
- Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.bioRxiv : the preprint server for biology · 2025Article
- Hyperactive 20Science advances · 2025Article
- Downregulation of USP9X in the DG Region of the Hippocampus Leads to AD-Like Cognitive Dysfunction in Mice.CNS neuroscience & therapeutics · 2025Article
- Synaptic proteins that aggregate and degrade slower with aging accumulate in microglia.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of hippocampal mossy fiber plasticity and episodic memory by human Aβ oligomers is prevented by enhancing cAMP signaling in Alzheimer's mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 4 countries.
Funding
Abstract
The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here, we investigate proteasome function and localization at synapses in Alzheimer's disease (AD) post-mortem brain tissue and in experimental models. We found a marked increase in ubiquitinylated proteins in post-mortem AD hippocampi compared to controls. Using several experimental models, we show that amyloid-β oligomers (AβOs) inhibit synaptic proteasome activity and trigger a reduction in synaptic proteasome content. We further show proteasome inhibition specifically in hippocampal synaptic fractions derived from APPswePS1ΔE9 mice. Reduced synaptic proteasome activity instigated by AβOs is corrected by treatment with rolipram, a phosphodiesterase-4 inhibitor, in mice. Results further show that dynein inhibition blocks AβO-induced reduction in dendritic proteasome content in hippocampal neurons. Finally, proteasome inhibition induces AD-like pathological features, including reactive oxygen species and dendritic spine loss in hippocampal neurons, inhibition of hippocampal mRNA translation, and memory impairment in mice. Results suggest that proteasome inhibition may contribute to synaptic and memory deficits in 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.