ArticleProceedings of the National Academy of Sciences of the United States of America2024
Inhibition of zDHHC7-driven protein S-palmitoylation prevents cognitive deficits in an experimental model of Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- AdipoRon's Impact on Alzheimer's Disease-A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Biliverdin reductase A deficiency reveals sex- and brain region-specific vulnerability to high-fat diet feeding.Redox biology · 2026Article
- Human amniotic mesenchymal stromal cell-derived extracellular vesicles reprogram microglia and prevent neurodegeneration in experimental models of Alzheimer's disease.Translational neurodegeneration · 2026Article
- Disease mechanisms and translational barriers guide nanocarrier design for nose to brain delivery in Alzheimer's disease.Discover nano · 2026Review
- Crosstalk between lipid metabolism and epigenetics in cellular senescence and age-related diseases.npj aging · 2026Review
- From lipid modification to cell death: the diverse roles of S-palmitoylation in cell fate decisions.Cell communication and signaling : CCS · 2026Review
- Intranasal administration of neural stem cell-derived extracellular vesicles prevents cognitive decline in both male and female 3×Tg-AD mice by dampening neuroinflammation and epigenetically regulating amyloid β metabolism.Alzheimer's research & therapy · 2026Article
- Palmitoylation of death receptor p75Alzheimer's research & therapy · 2026Article
- AI-enabled single-cell dissection of the palmitoylation landscape identifies a multicellular prognostic program in gastric cancer.NPJ precision oncology · 2026Article
- Sex-dependent rescue of memory and synaptic deficits in AD model mice by increasing PSD-95 palmitoylation.Communications biology · 2026Article
- S-palmitoylation in ferroptosis: molecular mechanisms, modulators, and interplay with autophagy.Apoptosis : an international journal on programmed cell death · 2026Review
- A Novel Palmitoylation-Related Molecular Signature for Predicting and Therapeutically Targeting Alzheimer's Disease.Molecular neurobiology · 2025Article
- Post-translational modifications regulating microglial inflammation in central nervous system disorders: a review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Cerebrospinal fluid proteomic signatures in cognitively normal individuals identify distinct clusters linked to neurodegeneration.Nature aging · 2025Article
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Protein palmitoylation: an emerging regulator of inflammatory signaling and diseases.Frontiers in immunology · 2025Review
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9 authors.
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Abstract
Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein S-palmitoylation in hippocampi of both 3×Tg-AD mice and post-mortem Alzheimer's disease (AD) patients. Chronic intranasal administration of the S-palmitoylation inhibitor 2-bromopalmitate counteracted synaptic plasticity and cognitive deficits, reduced the Aβ deposition in the hippocampus and extended the lifespan of both male and female 3×Tg-AD mice. Moreover, hippocampal silencing of zDHHC7 prevented the onset of cognitive deficits in the same experimental model. We also identified a FoxO1-mediated epigenetic mechanism inducing zDHHC7 expression, which was triggered by brain insulin resistance in 3×Tg-AD mice. Finally, in hippocampi of AD patients S-palmitoylation levels of Beta-Secretase 1 were associated with Aβ 1 to 42 load and they inversely correlated with Mini Mental State Examination scores. Our data reveal a key role of both zDHHC7 overexpression and protein hyperpalmitoylation in the onset and progression of AD-related alterations of synaptic plasticity and memory.
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