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

@article{Turner2003RolesOA,
  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},
  year={2003},
  volume={70},
  pages={1-32}
}
The amyloid precursor protein and postnatal neurogenesis/neuroregeneration.
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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Endogenous Regulators of Gamma-Secretase and Amyloid-Beta Production, and Engineering of Alzheimer"s Disease Therapeutic Tools
TLDR
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.
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References

SHOWING 1-10 OF 292 REFERENCES
Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives.
TLDR
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 (*)
TLDR
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
TLDR
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.
TLDR
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.
TLDR
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
TLDR
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
TLDR
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
TLDR
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.
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