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The Basic Biology of BACE1: A Key Therapeutic Target for Alzheimers Disease
Abstract
Alzheimer's disease (AD) is an intractable, neurodegenerative disease that appears to be brought about by both genetic and non-genetic factors. The neuropathology associated with AD is complex, although amyloid plaques composed of the beta-amyloid peptide (Abeta) are hallmark neuropathological lesions of AD brain. Indeed, Abeta plays an early and central role in this disease. beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the initiating enzyme in Abeta genesis and BACE1 levels are elevated under a variety of conditions. Given the strong correlation between Abeta and AD, and the elevation of BACE1 in this disease, this enzyme is a prime drug target for inhibiting Abeta production in AD. However, nine years on from the initial identification of BACE1, and despite intense research, a number of key questions regarding BACE1 remain unanswered. Indeed, drug discovery and development for AD continues to be challenging. While current AD therapies temporarily slow cognitive decline, treatments that address the underlying pathologic mechanisms of AD are completely lacking. Here we review the basic biology of BACE1. We pay special attention to recent research that has provided some answers to questions such as those involving the identification of novel BACE1 substrates, the potential causes of BACE1 elevation and the putative function of BACE1 in health and disease. Our increasing understanding of BACE1 biology should aid the development of compounds that interfere with BACE1 expression and activity and may lead to the generation of novel therapeutics for AD.
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“The BACE1 protein has four N‐linked glycosylation sites, which are targeted in the Golgi and facilitate pro‐peptide processing, maturation, and transportation.”
From BACE1: More than just a β‐secretase (2022) · cites this paper as [74]
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Circulating miRNAs as Biomarkers for Neurodegenerative Disorders
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The biosynthesis, signaling, and neurological functions of bile acids
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BACE1: More than just a β‐secretase
Taylor, H. A., Przemylska, L., Clavane, E. M., & Meakin, P. J. (2022) · Obesity Reviews · doi:10.1111/obr.13430 · Cited by 107
Increased BACE1-AS long noncoding RNA and β-amyloid levels in heart failure
Greco, S., Zaccagnini, G., Fuschi, P., Voellenkle, C., Carrara, M., Sadeghi, I., Bearzi, C., Maimone, B., Castelvecchio, S., Stellos, K., et al. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx013 · Cited by 94
Modulation of γ- and β-secretases as early prevention against Alzheimer's disease
Voytyuk, I., De Strooper, B., & Chávez-Gutiérrez, L. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.001 · Cited by 67
Metadata
- Authors
- Vassar, R., & Cole, S.
- Venue
- Current Genomics
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2007-12-01
- Volume
- 8
- Issue
- 8
- Pages
- 509-530
- ISSN
- 1389-2029
- PMC
- PMC2647160
- Cited by
- 84
- References
- 255
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.