ArticlePLoS genetics2013
Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype.Human molecular genetics · 2016Pooled it
- Harnessing Metabolism to Combat Neurodegeneration: Strategies for Reversing Age-Related Cognitive Decline.ACS pharmacology & translational science · 2025Review
- DSCR1 deficiency ameliorates the Aβ pathology of Alzheimer's disease by enhancing microglial activity.Life science alliance · 2023Article
- The Link between Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation in the Pathophysiology of Alzheimer's Disease: Therapeutic Implications and Future Perspectives.Antioxidants (Basel, Switzerland) · 2022Review
- The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at theFrontiers in synaptic neuroscience · 2022Article
- Minibrain kinase and calcineurin coordinate activity-dependent bulk endocytosis through synaptojanin.The Journal of cell biology · 2021Article
- Regulator of Calcineurin (RCAN): Beyond Down Syndrome Critical Region.Molecules and cells · 2020Review
- Mitochondria dysfunction in the pathogenesis of Alzheimer's disease: recent advances.Molecular neurodegeneration · 2020Review
- Genetic Dissection of Alzheimer's Disease UsingInternational journal of molecular sciences · 2020Review
- A Role forFrontiers in cellular neuroscience · 2019Article
- Calcineurin-Modulated Antimicrobial Peptide Expression Is Required for the Development ofFrontiers in physiology · 2019Article
- High-Amplitude Circadian Rhythms inGenetics · 2018Article
- Article
- DSCR1 is required for both axonal growth cone extension and steering.The Journal of cell biology · 2016Article
- The calcineurin inhibitor Sarah (Nebula) exacerbates Aβ42 phenotypes in a Drosophila model of Alzheimer's disease.Disease models & mechanisms · 2016Article
- Analysis of Amyloid Precursor Protein Function in Drosophila melanogaster.Frontiers in molecular neuroscience · 2016Review
- Loss of Polo ameliorates APP-induced Alzheimer's disease-like symptoms in Drosophila.Scientific reports · 2015Article
- Pharmocologic treatment with histone deacetylase 6 inhibitor (ACY-738) recovers Alzheimer's disease phenotype in amyloid precursor protein/presenilin 1 (APP/PS1) mice.Alzheimer's & dementia (New York, N. Y.) · 2015Article
- Bidirectional Regulation of Amyloid Precursor Protein-Induced Memory Defects by Nebula/DSCR1: A Protein Upregulated in Alzheimer's Disease and Down Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Dendritic and axonal mechanisms of Ca2+ elevation impair BDNF transport in Aβ oligomer-treated hippocampal neurons.Molecular biology of the cell · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Post-mortem brains from Down syndrome (DS) and Alzheimer's disease (AD) patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1), but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP), which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.
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.