BACE (β-secretase) modulates the processing of APLP2 in vivo

@article{Pastorino2004BACEM,
  title={BACE ($\beta$-secretase) modulates the processing of APLP2 in vivo},
  author={Lucia Pastorino and Annat F. Ikin and Smaragda Lamprianou and Nathalie Vacaresse and Jean-Pierre Revelli and Kenneth A. Platt and Paolo Paganetti and Paul M. Mathews and Sheila Harroch and Joseph D. Buxbaum},
  journal={Molecular and Cellular Neuroscience},
  year={2004},
  volume={25},
  pages={642-649}
}
Control of APP processing and Aβ generation level by BACE1 enzymatic activity and transcription
TLDR
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TLDR
During human BACE1 gene expression, ribosomes skipped some uAugs by leaky scanning and translated an upstream open reading frame, initiated efficiently at the fourth uAUG, and subsequently reinitiated Bace1 translation at the physiological AUG site, resulting in weak expression of B ACE1 under normal conditions.
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TLDR
It is concluded that therapeutic inhibition of BACE1 should be efficacious for AD, although careful titration of the drug dose may be necessary to limit mechanism-based side effects.
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TLDR
Analysis of knockout mice lacking the biosynthetic enzyme for bisecting GlcNAc, GnT‐III (Mgat3), revealed that cleavage of Aβ‐precursor protein (APP) by BACE1 is reduced in these mice, resulting in a decrease in Aβ plaques and improved cognitive function.
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TLDR
Current knowledge on BACE1 is presented, discussing its structure, function and complex regulation with a view to understanding Bace1 function in the brain, and BACE 1 as a target in blocking aberrant Aβ production in AD.
Bace1 modulates myelination in the central and peripheral nervous system
TLDR
It is shown that Bace1 regulates the process of myelination and myelin sheath thickness in the central and peripheral nerves and that processed neuregulin-1 regulates myelinations by means of phosphorylation of Akt in myelin-forming cells.
1 α-Secretase processing of the Alzheimer amyloid-β precursor protein and its homolog APLP 2
TLDR
The results show that the stimulated α-site cleavage of APP and APLP2 is regulated by different signaling pathways and that the cleavage is mediated by different enzymes.
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Expression of human β‐secretase in the mouse brain increases the steady‐state level of β‐amyloid
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