ArticleBrain structure & function2014
Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Aβ) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons.
Article in Brain structure & function, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer's disease.Nature communications · 2025Article
- Alzheimer's Disease and Frontotemporal Dementia: A Review of Pathophysiology and Therapeutic Approaches.Journal of neuroscience research · 2025Review
- Deletion of p75Frontiers in molecular neuroscience · 2023Article
- Hypocretin/orexin influences chronic sleep disruption injury in the hippocampus.Frontiers in aging neuroscience · 2022Article
- Integrated phylogeny of the human brain and pathobiology of Alzheimer's disease: A unifying hypothesis.Neuroscience letters · 2021Review
- Ablation of p75Translational psychiatry · 2021Article
- Long-distance regressive signaling in neural development and disease.Wiley interdisciplinary reviews. Developmental biology · 2021Review
- Elevated Levels of miR-144-3p Induce Cholinergic Degeneration by Impairing the Maturation of NGF in Alzheimer's Disease.Frontiers in cell and developmental biology · 2021Article
- Tuberous Sclerosis (tsc2+/-) Model Eker Rats Reveals Extensive Neuronal Loss with Microglial Invasion and Vascular Remodeling Related to Brain Neoplasia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Estradiol Replacement at the Critical Period Protects Hippocampal Neural Stem Cells to Improve Cognition in APP/PS1 Mice.Frontiers in aging neuroscience · 2020Article
- Removal of p75 Neurotrophin Receptor Expression from Cholinergic Basal Forebrain Neurons Reduces Amyloid-β Plaque Deposition and Cognitive Impairment in Aged APP/PS1 Mice.Molecular neurobiology · 2019Article
- Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors.Neuronal signaling · 2019Review
- Cellular Trafficking of Amyloid Precursor Protein in Amyloidogenesis Physiological and Pathological Significance.Molecular neurobiology · 2019Review
- Alleviation of Trigeminal Nociception Using p75 Neurotrophin Receptor Targeted Lentiviral Interference Therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Article
- Low-Affinity Neurotrophin Receptor p75 Promotes the Transduction of Targeted Lentiviral Vectors to Cholinergic Neurons of Rat Basal Forebrain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Article
- Cholinergic Mechanisms in the Cerebral Cortex: Beyond Synaptic Transmission.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2016Article
- Immunization Against Specific Fragments of Neurotrophin p75 Receptor Protects Forebrain Cholinergic Neurons in the Olfactory Bulbectomized Mice.Journal of Alzheimer's disease : JAD · 2016Article
- Interactions between Aβ oligomers and presynaptic cholinergic signaling: age-dependent effects on attentional capacities.Behavioural brain research · 2014Article
- The type of Aβ-related neuronal degeneration differs between amyloid precursor protein (APP23) and amyloid β-peptide (APP48) transgenic mice.Acta neuropathologica communications · 2013Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
A fascinating yet perhaps overlooked trait of the p75 neurotrophin receptor (p75(NTR)) is its ability to bind ligands with no obvious neurotrophic function. Using cultured basal forebrain (BF) neurons, this study demonstrates selective internalization of amyloid β (Aβ) 1-42 in conjunction with p75(NTR) (labelled with IgG192-Cy3) by cholinergic cells. Active under resting conditions, this process was enhanced by high K(+) stimulation and was insensitive to inhibitors of regulated synaptic activity-tetrodotoxin or botulinum neurotoxins (BoNT type/A and/B). Blockade of sarco-endoplasmic reticulum (SERCA) Ca(2+) ATPase with thapsigargin and CPA or chelation of Ca(2+) with EGTA-AM strongly suppressed the endocytosis of p75(NTR), implicating the role of ER released Ca(2+). The uptake of IgG192-Cy3 was also reduced by T-type Ca(2+) channel blocker mibefradil but not Cd(2+), an indiscriminate blocker of high voltage-activated Ca(2+) currents. A strong co-localization of IgG192-Cy3 with late endosome (Rab7) or lysosome (Lamp1) qualifier proteins suggest these compartments as the primary destination for internalized IgG192 and Aβ. Selective uptake and labeling of BF cholinergic cells with IgG192-Cy3 injected into the prefrontal cortex was verified also in vivo. The significance of these findings in relation to Aβ clearance in the cerebral cortex and pathophysiology of Alzheimer's disease is discussed.
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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.