ArticleeLife2020
Presynaptic APP levels and synaptic homeostasis are regulated by Akt phosphorylation of huntingtin.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Post-Translational Modifications of Huntingtin: Mechanistic Insights and Therapeutic Opportunities in Huntington's Disease.International journal of molecular sciences · 2025Review
- Zinc and copper effect mechanical cell adhesion properties of the amyloid precursor protein.Biological chemistry · 2024Article
- Roscovitine, a CDK Inhibitor, Reduced Neuronal Toxicity of mHTT by Targeting HTT Phosphorylation at S1181 and S1201 In Vitro.International journal of molecular sciences · 2024Article
- Non-canonical function of ADAM10 in presynaptic plasticity.Cellular and molecular life sciences : CMLS · 2024Article
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- Article
- The HSPB1-p62/SQSTM1 functional complex regulates the unconventional secretion and transcellular spreading of the HD-associated mutant huntingtin protein.Human molecular genetics · 2023Article
- Disruption of axonal transport in neurodegeneration.The Journal of clinical investigation · 2023Review
- Huntingtin S421 phosphorylation increases kinesin and dynein engagement on early endosomes and lysosomes.Biophysical journal · 2023Article
- Failure to Thrive: Impaired BDNF Transport along the Cortical-Striatal Axis in Mouse Q140 Neurons of Huntington's Disease.Biology · 2023Article
- Selective motor activation in organelle transport along axons.Nature reviews. Molecular cell biology · 2022Review
- A pathogenic proteolysis-resistant huntingtin isoform induced by an antisense oligonucleotide maintains huntingtin function.JCI insight · 2022Article
- Altered m6A RNA methylation contributes to hippocampal memory deficits in Huntington's disease mice.Cellular and molecular life sciences : CMLS · 2022Article
- CaInternational journal of molecular sciences · 2022Review
- Selective Activation of CNS and ReferenceInternational journal of molecular sciences · 2021Article
- Recreating mouse cortico-hippocampal neuronal circuit in microfluidic devices to study BDNF axonal transport upon glucocorticoid treatment.STAR protocols · 2021Article
- Huntingtin and the Synapse.Frontiers in cellular neuroscience · 2021Review
- The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence.Frontiers in nutrition · 2021Article
- Excess Rab4 rescues synaptic and behavioral dysfunction caused by defective HTT-Rab4 axonal transport in Huntington's disease.Acta neuropathologica communications · 2020Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Studies have suggested that amyloid precursor protein (APP) regulates synaptic homeostasis, but the evidence has not been consistent. In particular, signaling pathways controlling APP transport to the synapse in axons and dendrites remain to be identified. Having previously shown that Huntingtin (HTT), the scaffolding protein involved in Huntington's disease, regulates neuritic transport of APP, we used a microfluidic corticocortical neuronal network-on-a-chip to examine APP transport and localization to the pre- and post-synaptic compartments. We found that HTT, upon phosphorylation by the Ser/Thr kinase Akt, regulates APP transport in axons but not dendrites. Expression of an unphosphorylatable HTT decreased axonal anterograde transport of APP, reduced presynaptic APP levels, and increased synaptic density. Ablating in vivo HTT phosphorylation in APPPS1 mice, which overexpress APP, reduced presynaptic APP levels, restored synapse number and improved learning and memory. The Akt-HTT pathway and axonal transport of APP thus regulate APP presynaptic levels and synapse homeostasis.
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.