ArticleAging cell2016
NGF controls APP cleavage by downregulating APP phosphorylation at Thr668: relevance for Alzheimer's disease.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Roles of lactate and protein lactylation in neurogenesis and neurodegenerative disease.Journal of translational medicine · 2026Review
- Amyloid Precursor Protein Processing Links Female Urgency Urinary Incontinence with Alzheimer's Disease: Implications for Treatment.International journal of molecular sciences · 2026Article
- Deep brain stimulation of the nucleus basalis of Meynert in neurodegenerative diseases with cognitive impairment: An update on evidence and mechanisms.Neural regeneration research · 2026Article
- Post-translational modifications in alzheimer's disease: proteome dynamics and emerging therapeutic strategies.Metabolic brain disease · 2026Review
- Advances in JNK inhibitor development: therapeutic prospects in neurodegenerative diseases and fibrosis.Archives of pharmacal research · 2025Review
- From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.Medicina (Kaunas, Lithuania) · 2025Review
- Nerve growth factor: what can surgeons and oncologists learn from a neurological and psychological biomarker?Molecular medicine (Cambridge, Mass.) · 2025Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Alzheimer's Disease and Frontotemporal Dementia: A Review of Pathophysiology and Therapeutic Approaches.Journal of neuroscience research · 2025Review
- Pathway-based network medicine identifies novel natural products for Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.Signal transduction and targeted therapy · 2024Review
- GSK3: A potential target and pending issues for treatment of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Review
- ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides.FEBS open bio · 2024Article
- Review
- All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease.Neural regeneration research · 2022Review
- Development and Biological Characterization of a Novel Selective TrkA Agonist with Neuroprotective Properties against Amyloid Toxicity.Biomedicines · 2022Article
- Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential.Translational neurodegeneration · 2022Review
- Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NGF has been implicated in forebrain neuroprotection from amyloidogenesis and Alzheimer's disease (AD). However, the underlying molecular mechanisms are still poorly understood. Here, we investigated the role of NGF signalling in the metabolism of amyloid precursor protein (APP) in forebrain neurons using primary cultures of septal neurons and acute septo-hippocampal brain slices. In this study, we show that NGF controls the basal level of APP phosphorylation at Thr668 (T668) by downregulating the activity of the Ser/Thr kinase JNK(p54) through the Tyr kinase signalling adaptor SH2-containing sequence C (ShcC). We also found that the specific NGF receptor, Tyr kinase A (TrkA), which is known to bind to APP, fails to interact with the fraction of APP molecules phosphorylated at T668 (APP(pT668) ). Accordingly, the amount of TrkA bound to APP is significantly reduced in the hippocampus of ShcC KO mice and of patients with AD in which elevated APP(pT668) levels are detected. NGF promotes TrkA binding to APP and APP trafficking to the Golgi, where APP-BACE interaction is hindered, finally resulting in reduced generation of sAPPβ, CTFβ and amyloid-beta (1-42). These results demonstrate that NGF signalling directly controls basal APP phosphorylation, subcellular localization and BACE cleavage, and pave the way for novel approaches specifically targeting ShcC signalling and/or the APP-TrkA interaction in AD therapy.
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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.