ArticleAging cell2012
Tyr682 in the Aβ-precursor protein intracellular domain regulates synaptic connectivity, cholinergic function, and cognitive performance.
Article in Aging cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Real-time heterogeneity of supramolecular assembly of amyloid precursor protein is modulated by an endocytic risk factor PICALM.Cellular and molecular life sciences : CMLS · 2023Article
- Age-dependent NMDA receptor function is regulated by the amyloid precursor protein.Aging cell · 2023Article
- Alzheimer's disease: Pathophysiology and dental pulp stem cells therapeutic prospects.Frontiers in cell and developmental biology · 2022Review
- Article
- Might Fibroblasts from Patients with Alzheimer's Disease Reflect the Brain Pathology? A Focus on the Increased Phosphorylation of Amyloid Precursor Protein TyrBrain sciences · 2021Article
- Article
- Amyloid, APP, and Electrical Activity of the Brain.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2020Review
- Article
- Phosphorylation Signaling in APP Processing in Alzheimer's Disease.International journal of molecular sciences · 2019Review
- Regulation of Neurotransmitter Release by Amyloid Precursor Protein Through Synapsin Phosphorylation.Neurochemical research · 2019Article
- Small Molecule Amyloid-β Protein Precursor Processing Modulators Lower Amyloid-β Peptide Levels via cKit Signaling.Journal of Alzheimer's disease : JAD · 2019Article
- The Intersection of NGF/TrkA Signaling and Amyloid Precursor Protein Processing in Alzheimer's Disease Neuropathology.International journal of molecular sciences · 2017Review
- Not just amyloid: physiological functions of the amyloid precursor protein family.Nature reviews. Neuroscience · 2017Review
- Impaired NGF/TrkA Signaling Causes Early AD-Linked Presynaptic Dysfunction in Cholinergic Primary Neurons.Frontiers in cellular neuroscience · 2017Article
- An Aberrant Phosphorylation of Amyloid Precursor Protein Tyrosine Regulates Its Trafficking and the Binding to the Clathrin Endocytic Complex in Neural Stem Cells of Alzheimer's Disease Patients.Frontiers in molecular neuroscience · 2017Article
- Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer's Disease Patients Carrying the APOE Epsilon 4 Allele.Neural plasticity · 2017Article
- Amyloid Precursor Protein (APP) May Act as a Substrate and a Recognition Unit for CRL4CRBN and Stub1 E3 Ligases Facilitating Ubiquitination of Proteins Involved in Presynaptic Functions and Neurodegeneration.The Journal of biological chemistry · 2016Article
- NGF controls APP cleavage by downregulating APP phosphorylation at Thr668: relevance for Alzheimer's disease.Aging cell · 2016Article
- Behavioural studies on the ethanol leaf extract of Grewia carpinifolia in Wistar rats.African health sciences · 2016Article
- New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies.International journal of molecular sciences · 2015Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Processing of Aβ-precursor protein (APP) plays an important role in Alzheimer's disease (AD) pathogenesis. The APP intracellular domain contains residues important in regulating APP function and processing, in particular the 682YENPTY687 motif. To dissect the functions of this sequence in vivo, we created an APP knock-in allele mutating Y682 to Gly (APP(YG/YG) mice). This mutation alters the processing of APP and TrkA signaling and leads to postnatal lethality and neuromuscular synapse defects when expressed on an APP-like protein 2 KO background. This evidence prompted us to characterize further the APP(YG/YG) mice. Here, we show that APP(YG/YG) mice develop aging-dependent decline in cognitive and neuromuscular functions, a progressive reduction in dendritic spines, cholinergic tone, and TrkA levels in brain regions governing cognitive and motor functions. These data are consistent with our previous findings linking NGF and APP signaling and suggest a causal relationship between altered synaptic connectivity, cholinergic tone depression and TrkA signaling deficit, and cognitive and neuromuscular decline in APP(YG/YG) mice. The profound deficits caused by the Y682 mutation underscore the biological importance of APP and indicate that APP(YG/YG) are a valuable mouse model to study APP functions in physiological and pathological processes.
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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.