ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Increasing Tip60 HAT levels rescues axonal transport defects and associated behavioral phenotypes in a Drosophila Alzheimer's disease model.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
- Epigenetic Modulation Is a Key Mechanism in Cognitive Deficit: Unveiling Garcinol as a Potent HAT Inhibitor in Improving Alzheimer's Disease.ACS omega · 2026Review
- Review
- Tip60 HAT activators as therapeutic modulators for Alzheimer's disease.Nature communications · 2025Article
- Lysine Acetyltransferase TIP60 Restricts Nerve Injury by Activating IKKβ/SNAP23 Axis-Mediated Autophagosome-Lysosome Fusion in Alzheimer's Disease.CNS neuroscience & therapeutics · 2024Article
- Novel histone post-translational modifications in Alzheimer's disease: current advances and implications.Clinical epigenetics · 2024Review
- Alzheimer's Disease-Related Epigenetic Changes: Novel Therapeutic Targets.Molecular neurobiology · 2024Review
- Histone acetylation in an Alzheimer's disease cell model promotes homeostatic amyloid-reducing pathways.Acta neuropathologica communications · 2024Article
- Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control.Molecular and cellular neurosciences · 2023Article
- Tip60's Novel RNA-Binding Function Modulates Alternative Splicing of Pre-mRNA Targets Implicated in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Role of primary aging hallmarks in Alzheimer´s disease.Theranostics · 2023Review
- Tip60/Kat5 may be a novel candidate histone acetyltransferase for the regulation of liver iron localization via acetylation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Article
- Metabolic disorder in Alzheimer's disease.Metabolic brain disease · 2021Review
- Disruption of Tip60 HAT mediated neural histone acetylation homeostasis is an early common event in neurodegenerative diseases.Scientific reports · 2020Article
- Article
- Targeted Downregulation ofJournal of Korean medical science · 2019Article
- Article
- Restoring Tip60 HAT/HDAC2 Balance in the Neurodegenerative Brain Relieves Epigenetic Transcriptional Repression and Reinstates Cognition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- The Epigenetics of Alzheimer's Disease: Factors and Therapeutic Implications.Frontiers in genetics · 2018Review
- Impact of a discordant helix on β-amyloid structure, aggregation ability and toxicity.European biophysics journal : EBJ · 2017Review
- Neural Circuits Underlying Fly Larval Locomotion.Current pharmaceutical design · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Axonal transport defects and axonopathy are prominent in early preclinical stages of Alzheimer's disease (AD), often preceding known disease-related pathology by over a year. As epigenetic transcriptional regulatory mechanisms, such as histone acetylation, are critical for neurogenesis, it is postulated that their misregulation might be linked to early pathophysiological mechanisms that contribute to AD. The histone acetyltransferase (HAT) Tip60 epigenetically regulates genes enriched for neuronal functions and is implicated in AD via its formation of a transcriptional regulatory complex with the amyloid precursor protein (APP) intracellular domain. Disruption of APP function is associated with axonal transport defects, raising the possibility that an epigenetic role for Tip60 might also be involved. Here, we examine whether Tip60 HAT activity functions in axonal transport using Drosophila CNS motor neurons as a well-characterized transport model. We show that reduction of Tip60 HAT activity in the nervous system causes axonopathy and transport defects associated with epigenetic misregulation of certain axonal transport-linked Tip60 target genes. Functional consequences of these defects are evidenced by reduced locomotion activity of the mutant Tip60 larvae, and these phenotypes can be partially rescued with certain histone deacetylase inhibitors. Finally, we demonstrate that Tip60 function in axonal transport is mediated by APP and that, remarkably, excess Tip60 exerts a neuroprotective role in APP-induced axonal transport and functional locomotion defects. Our observations highlight a novel functional interactive role between Tip60 HAT activity and APP in axonal transport and provide insight into the importance of specific HAT modulators for cognitive disorder treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.