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} }
106 Citations
Control of APP processing and Aβ generation level by BACE1 enzymatic activity and transcription
- BiologyFASEB journal : official publication of the Federation of American Societies for Experimental Biology
- 2006
It is demonstrated that lower BACE transcription is responsible for the minority of APP undergoing the amyloidogenic pathway and relatively lower Aβ production in the normal conditions, and that a slight increase in BACE1 can induce a dramatic elevation in A β production, indicating that the increase in FASEB can potentially increase neuritic plaque formation in the pathological condition.
BACE2 plays a role in the insulin receptor trafficking in pancreatic ß-cells.
- Biology, MedicineAmerican journal of physiology. Endocrinology and metabolism
- 2010
BACE2 is presented as an important enzyme in β-cell function as a role for BACE2 in the IRβ trafficking and insulin signaling in human pancreas.
Leaky Scanning and Reinitiation Regulate BACE1 Gene Expression
- BiologyAlzheimer's & Dementia
- 2006
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.
The β-secretase enzyme BACE1 as a therapeutic target for Alzheimer's disease
- Biology, ChemistryAlzheimer's Research & Therapy
- 2011
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.
An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer's disease
- Biology, ChemistryEMBO molecular medicine
- 2015
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.
Understanding BACE1: essential protease for amyloid-β production in Alzheimer’s disease
- BiologyCellular and Molecular Life Sciences
- 2008
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
- Biology, ChemistryNature Neuroscience
- 2006
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
- Biology
- 2013
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.
Transcriptional and translational regulation of BACE1 expression—Implications for Alzheimer's disease
- BiologyProgress in Neurobiology
- 2006
References
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It is established that BACE1 is the principal neuronal protease required to cleave APP at +1 and +11 sites that generate N-termini of Aβ.
ASP1 (BACE2) Cleaves the Amyloid Precursor Protein at the β-Secretase Site
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The characterization of a second highly related aspartic proteinase, Asp1, is described as a second β-secretase candidate and has the N-terminal sequence ALEP… , indicating that it has lost the prodomain.
BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics.
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The abundance of A beta 11-40/42 produced by BACE suggests that their roles in AD pathogenesis may be underestimated, and BACE utilizes both full-length APP as well as C99 as substrates for the production of C89.
Expression of human β‐secretase in the mouse brain increases the steady‐state level of β‐amyloid
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In mice expressing huBACE in addition to human APP wild‐type or carrying the Swedish mutation, the induction of APP processing characterized by elevated C99, C89 and sAPPβ, results in increased brain levels of β‐amyloid peptides Aβ40 and Aβ42 at steady‐state.