ArticleThe Journal of biological chemistry2013
The amyloid precursor protein (APP) triplicated gene impairs neuronal precursor differentiation and neurite development through two different domains in the Ts65Dn mouse model for Down syndrome.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives.Frontiers in cellular neuroscience · 2022Review
- Intellectual disability: dendritic anomalies and emerging genetic perspectives.Acta neuropathologica · 2021Review
- Astrocytes in Down Syndrome Across the Lifespan.Frontiers in cellular neuroscience · 2021Review
- Signalling Pathways Implicated in Alzheimer's Disease Neurodegeneration in Individuals with and without Down Syndrome.International journal of molecular sciences · 2020Review
- Review
- Physiological and pathological effects of amyloid-β species in neural stem cell biology.Neural regeneration research · 2019Review
- Epigenetic signatures of methylated DNA cytosine in Alzheimer's disease.Science advances · 2019Article
- Down syndrome mouse models have an abnormal enteric nervous system.JCI insight · 2019Article
- Abnormal development of the inferior temporal region in fetuses with Down syndrome.Brain pathology (Zurich, Switzerland) · 2018Article
- Role of Amyloid Precursor Protein (APP) and Its Derivatives in the Biology and Cell Fate Specification of Neural Stem Cells.Molecular neurobiology · 2018Review
- Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond.International journal of molecular sciences · 2018Review
- The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons.Stem cell reports · 2018Article
- Rodent models in Down syndrome research: impact and future opportunities.Disease models & mechanisms · 2017Review
- Expression of TAG1/APP signaling pathway in the proliferation and differentiation of glioma stem cells.Oncology letters · 2017Article
- Long-term effect of neonatal inhibition of APP gamma-secretase on hippocampal development in the Ts65Dn mouse model of Down syndrome.Neurobiology of disease · 2017Article
- Altered neurogenesis in mouse models of Alzheimer disease.Neurogenesis (Austin, Tex.) · 2017Review
- Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome.Current Alzheimer research · 2016Review
- Genome-wide miR-155 and miR-802 target gene identification in the hippocampus of Ts65Dn Down syndrome mouse model by miRNA sponges.BMC genomics · 2015Article
- New Perspectives for the Rescue of Cognitive Disability in Down Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Inhibition of APP gamma-secretase restores Sonic Hedgehog signaling and neurogenesis in the Ts65Dn mouse model of Down syndrome.Neurobiology of disease · 2015Article
Corrections and comments
- Retraction · 2020-03-06Duplication of/in Image · Error in Image ·
- Retracted
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intellectual disability in Down syndrome (DS) appears to be related to severe proliferation impairment during brain development. Recent evidence shows that it is not only cellular proliferation that is heavily compromised in DS, but also cell fate specification and dendritic maturation. The amyloid precursor protein (APP), a gene that is triplicated in DS, plays a key role in normal brain development by influencing neural precursor cell proliferation, cell fate specification, and neuronal maturation. APP influences these processes via two separate domains, the APP intracellular domain (AICD) and the soluble secreted APP. We recently found that the proliferation impairment of neuronal precursors (NPCs) from the Ts65Dn mouse model for DS was caused by derangement of the Shh pathway due to overexpression of patched1(Ptch1), its inhibitory regulator. Ptch1 overexpression was related to increased levels within the APP/AICD system. The overall goal of this study was to determine whether APP contributes to neurogenesis impairment in DS by influencing in addition to proliferation, cell fate specification, and neurite development. We found that normalization of APP expression restored the reduced neuronogenesis, the increased astrogliogenesis, and the reduced neurite length of trisomic NPCs, indicating that APP overexpression underpins all aspects of neurogenesis impairment. Moreover, we found that two different domains of APP impair neuronal differentiation and maturation in trisomic NPCs. The APP/AICD system regulates neuronogenesis and neurite length through the Shh pathway, whereas the APP/secreted AP system promotes astrogliogenesis through an IL-6-associated signaling cascade. These results provide novel insight into the mechanisms underlying brain development alterations in DS.
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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.