Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory

  title={Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory},
  author={Paul R. Turner and Kathleen D. O’Connor and Warren P Tate and Wickliffe C. Abraham},
  journal={Progress in Neurobiology},
The amyloid precursor protein and postnatal neurogenesis/neuroregeneration.
Amyloid precursor protein: cellular studies and animal models
It is found that antibody-bound APP upregulates expression of ornithine decarboxylase (ODC), which is the initial and rate-controlling enzyme in polyamine biosynthesis, and demonstrated that ODC translocates in AD, from the nuclear compartment towards the cytoplasmic.
The human β-amyloid precursor protein: biomolecular and epigenetic aspects
An overview of the current understanding of Beta-amyloid precursor protein, including its structure, expression patterns, proteolytic processing and putative functions is provided, and recent data concerning its epigenetic regulation, especially in alternative APP pre-mRNA splicing and in the control of genomic rearrangements of the APP gene are reported.
The physiological processing of Alzheimer-associated amyloid beta precursor protein in human and animal-derived neuronal models
It is found that APP is differentially processed depending on neuronal and synaptic maturation and presented a platform for future studies targeting APP/Aβ function and dysfunction.
Investigation of secreted amyloid precursor protein-α binding partners
A protein pull-down approach was used to isolate and characterise putative receptor(s) and any intracellular binding proteins in sAPPα, findinghibitin and HMGB1 provide the most likely candidates for transducing the effects of sAPP α.
Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα
These studies have revealed that either upregulating α-secretase activity, acutely administering APPs α or chronic delivery of APPsα via a gene therapy approach can effectively treat mouse models of Alzheimer’s disease (AD) and other disorders such as traumatic head injury.
Netrin-1 interacts with amyloid precursor protein and regulates amyloid-β production
It is shown that APP binds netrin-1, a multifunctional guidance and trophic factor that modulates APP signaling triggering APP intracellular domain (AICD)-dependent gene transcription and suppresses Aβ peptide production in brain slices from Alzheimer model transgenic mice.
Endogenous Regulators of Gamma-Secretase and Amyloid-Beta Production, and Engineering of Alzheimer"s Disease Therapeutic Tools
The first part of this thesis work focused on endogenous modulation of gamma-secretase, and its consequences on actin cytoskeleton dynamics, and discovered a gamma- secretase-dependent regulation of the binding of Cofilin to actin filaments.


Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives.
Alternative enzymatic processing of beta-APP liberates A beta, which has a propensity to form amyloid fibrils; A beta can damage and kill neurons and increase their vulnerability to excitotoxicity.
APP-BP1, a Novel Protein That Binds to the Carboxyl-terminal Region of the Amyloid Precursor Protein (*)
The cloning of a cDNA encoding a ubiquitously expressed 59-kDa APP-binding protein, called APP-BP1, is 61% similar to a protein encoded by the Arabidopsis AXR1 gene, required for normal response to the hormone auxin, and is a relative of the ubiquitin activating enzyme E1.
Beta-amyloid-related peptides inhibit potassium-evoked acetylcholine release from rat hippocampal slices
Results demonstrate that APP-derived A beta-related peptides can regulate the release of endogenous acetylcholine potently by acting on cholinergic terminals, and suggests a potential mechanistic link between the deposition of A beta and the preferential vulnerability of certain Cholinergic projections in AD.
The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain.
It is concluded that the pathogenically critical process of Abeta oligomers, principally dimers, in primary human neurons and in neuronal and nonneural cell lines begins intraneuronally.
The amyloid precursor protein is developmentally regulated and correlated with synaptogenesis.
It is shown, in the primary visual pathway of the hamster, that APPs are developmentally regulated proteins rapidly transported to the growing tips of nerve fibers, suggesting that target recognition and synaptic contact may result in a signal for APP cleavage in the CNS in vivo.
Increase of synaptic density and memory retention by a peptide representing the trophic domain of the amyloid beta/A4 protein precursor.
  • J. RochE. Masliah T. Saitoh
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
It is reported here that a 17-mer peptide, containing this active domain of sAPP, can induce cellular and behavioral changes when infused into rat brains and this results suggest that APP is involved in memory retention through its effect on synaptic structure.
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
An apparently full-length complementary DNA clone coding for the A4 polypeptide is isolated and sequenced and suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo
It is reported that natural oligomers of human Aβ are formed soon after generation of the peptide within specific intracellular vesicles and are subsequently secreted from the cell, indicating that synaptotoxic Aβ oligomers can be targeted therapeutically.