The DOI matches its Crossref record; 255 of the 255 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
2 retracted
Items 201–255 of 255
β-Site APP Cleaving Enzyme mRNA Expression in APP Transgenic Mice
Irizarry, M. C., Locascio, J. J., & Hyman, B. T. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63955-7 · Cited by 69
Rapoport, S. I. (1999) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/pl00014174 · Cited by 69
Apical Sorting of β-Secretase Limits Amyloid β-Peptide Production
Capell, A., Meyn, L., Fluhrer, R., Teplow, D. B., Walter, J., & Haass, C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109119200 · Cited by 68
Detection of a Soluble Form of BACE-1 in Human Cerebrospinal Fluid by a Sensitive Activity Assay
Verheijen, J. H., Huisman, L. G. M., van Lent, N., Neumann, U., Paganetti, P., Hack, C. E., Bouwman, F. H., Lindeman, J. H. N., Bollen, E. L. E. M., & Hanemaaijer, R. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2006.066720 · Cited by 67
Lleó, A., Waldron, E., Arnim, C. A. F. V., Herl, L. D., Tangredi, M. M., Peltan, I. D., Strickland, D. K., Koo, E. H., Hyman, B. T., Pietrzik, C. U., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413969200 · Cited by 66
Increased BACE1 maturation contributes to the pathogenesis of Alzheimer's disease in Down syndrome
Sun, X., Tong, Y., Qing, H., Chen, C.-H., & Song, W. (2006) · The FASEB Journal · doi:10.1096/fj.05-5628com · Cited by 65
Caspase-Mediated Degeneration in Alzheimer's Disease
Cribbs, D. H., Poon, W. W., Rissman, R. A., & Blurton-Jones, M. M. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63302-0 · Cited by 64
Harada, H., Tamaoka, A., Ishii, K., Shoji, S., Kametaka, S., Kametani, F., Saito, Y., & Murayama, S. (2005) · Neuroscience Research · doi:10.1016/j.neures.2005.10.001 · Cited by 64
Fluhrer, R., Multhaup, G., Schlicksupp, A., Okochi, M., Takeda, M., Lammich, S., Willem, M., Westmeyer, G., Bode, W., Walter, J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211485200 · Cited by 64
Vascular disorder in Alzheimer’s disease: role in pathogenesis of dementia and therapeutic targets
Zloković, B. V. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00150-3 · Cited by 63
PAR-4 Is Involved in Regulation of β-Secretase Cleavage of the Alzheimer Amyloid Precursor Protein
Xie, J., & Guo, Q. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411933200 · Cited by 61
Hussain, I., Hawkins, J., Shikotra, A., Riddell, D. R., Faller, A., & Dingwall, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304186200 · Cited by 61
GGA1 Acts as a Spatial Switch Altering Amyloid Precursor Protein Trafficking and Processing
Arnim, C. A. F. V., Spoelgen, R., Peltan, I. D., Deng, M., Courchesne, S. L., Koker, M., Matsui, T., Kowa, H., Lichtenthaler, S. F., Irizarry, M. C., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2290-06.2006 · Cited by 59
Rapoport, S. I., Horwitz, B., Grady, C. L., Haxby, J. V., DeCarli, C. S., & Schapiro, M. B. (1991) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5931-9_18 · Cited by 59
Bodendorf, U., Fischer, F., Bodian, D., Multhaup, G., & Paganetti, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008861200 · Cited by 58
Hypertension and Related Factors in the Etiology of Alzheimer's Disease
Skoog, I. G., & Gustafson, D. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04796.x · Cited by 58
Presenilin/γ‐secretase activity regulates protein clearance from the endocytic recycling compartment
Zhang, M., Haapasalo, A., Kim, D. Y., Ingano, L. A. M., Pettingell, W. H., & Kovacs, D. M. (2006) · The FASEB Journal · doi:10.1096/fj.05-5531fje · Cited by 58
Cloning and expression of the rat BACE1 promoter
Lange‐Dohna, C., Zeitschel, U., Gaunitz, F., Perez-Polo, J. R., Bigl, V., & Roßner, S. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10639 · Cited by 56
Sheng, J. G., Price, D. L., & Koliatsos, V. E. (2003) · Experimental Neurology · doi:10.1016/j.expneurol.2003.08.018 · Cited by 56
Insights into the Phosphoregulation of β‐Secretase Sorting Signal by the VHS Domain of GGA1
Shiba, T., Kametaka, S., Kawasaki, M., Shibata, M., Waguri, S., Uchiyama, Y., & Wakatsuki, S. (2004) · Traffic · doi:10.1111/j.1600-0854.2004.00188.x · Cited by 56
Expression of β-secretase mRNA in transgenic Tg2576 mouse brain with Alzheimer plaque pathology
Bigl, M., Apelt, J., Luschekina, E. A., Lange‐Dohna, C., Roßner, S., & Schliebs, R. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01452-x · Cited by 55
Züchner, T., Perez-Polo, J. R., & Schliebs, R. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20152 · Cited by 55
Leuba, G., Wernli, G., Vernay, A., Kraftsik, R., Mohajeri, M. H., & Saini, K. (2005) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000083496 · Cited by 54
Ge, Y., Maloney, B., Sambamurti, K., & Lahiri, D. K. (2004) · The FASEB Journal · doi:10.1096/fj.03-1379fje · Cited by 54
Sauder, J. M., Arthur, J. W., & Dunbrack, R. L. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3860 · Cited by 52
Proteomics‐driven progress in neurodegeneration research
Fountoulakis, M., & Κοσσίδα, Σ. (2006) · Electrophoresis · doi:10.1002/elps.200500738 · Cited by 52
Tanahashi, H., & Tabira, T. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01912-7 · Cited by 51
Splice variants of the β-site APP-cleaving enzyme BACE1 in human brain and pancreas
Ehehalt, R., Michel, B., De Pietri Tonelli, D., Zacchetti, D., Simons, K., & Keller, P. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00169-9 · Cited by 51
Parsons, R. B., Price, G. C., Farrant, J. K., Subramaniam, D., Adeagbo-Sheikh, J., & Austen, B. (2006) · Biochemical Journal · doi:10.1042/bj20060655 · Cited by 50
Closing in on the Amyloid Cascade
Doms, R. W., & Huse, J. T. (2000) · Molecular Neurobiology · doi:10.1385/mn:22:1-3:081 · Cited by 50
Severe cardiovascular disease and Alzheimer's disease: Senile plaque formation in cortical areas
Soneira, C. F., & Scott, T. M. (1996) · Clinical Anatomy · doi:10.1002/(sici)1098-2353(1996)9:2<118::aid-ca4>3.0.co;2-d · Cited by 48
The genetics of Alzheimer's disease
Rubinsztein, D. C. (1997) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00014-2 · Cited by 48
The BACE gene: genomic structure and candidate gene study in late-onset Alzheimer's disease
Murphy, T., Yip, A. G., Brayne, C., Easton, D. F., Evans, J. G., Xuereb, J. H., Cairns, N. J., Esiri, M. M., & Rubinsztein, D. C. (2001) · Neuroreport · doi:10.1097/00001756-200103050-00040 · Cited by 48
Gold, G., Blouin, J., Herrmann, F. R., Michon, A., Mulligan, R., Saïl, G. D., Bouras, C., Giannakopoulos, P., & Antonarakis, S. E. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10010 · Cited by 46
Association studies using novel polymorphisms in BACE1 and BACE2
Nowotny, P., Kwon, J. M., Chakraverty, S., Nowotny, V., Morris, J. C., & Goate, A. (2001) · Neuroreport · doi:10.1097/00001756-200107030-00008 · Cited by 44
Huse, J. T., Byant, D., Yang, Y., Pijak, D. S., D’Souza, I., Lah, J. J., Lee, V. M. ‐., Doms, R. W., & Cook, D. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213303200 · Cited by 43
Prodomain processing of Asp1 (BACE2) is autocatalytic
Hussain, I., Christie, G., Schneider, K., Moore, S., & Dingwall, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101069200 · Cited by 41
Clarimón, J., Bertranpetit, J., Calafell, F., Boada, M., T�rraga, L., & Comas, D. (2003) · Journal of Neurology · doi:10.1007/s00415-003-1127-8 · Cited by 41
BACE1 modulates filopodia-like protrusions induced by sodium channel β4 subunit
Miyazaki, H., Oyama, F., Wong, H. K., Kaneko, K., Sakurai, T., Tamaoka, A., & Nukina, N. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.06.170 · Cited by 40
Wickham, L., Benjannet, S., Marcinkiewicz, E., Chrétien, M., & Seidah, N. G. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02840.x · Cited by 38
The Functions of the Amyloid Precursor Protein Gene
Panegyres, P. K. (2001) · Reviews in the Neurosciences · doi:10.1515/revneuro.2001.12.1.1 · Cited by 36
Polymorphism in the BACE gene influences the risk for Alzheimer's disease
Kirschling, C. M., Kölsch, H., Frahnert, C., Rao, M. L., Maier, W., & Heun, R. (2003) · Neuroreport · doi:10.1097/00001756-200307010-00011 · Cited by 36
Yan, X., Xiong, K., Luo, X., Struble, R. G., & Clough, R. W. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21239 · Cited by 34
Volume cerebral blood flow reduction in pre-clinical stage of Alzheimer disease:
Akkawi, N. M., Borroni, B., Agosti, C., Magoni, M., Broli, M., Pezzini, A., & Padovani, A. (2005) · Journal of Neurology · doi:10.1007/s00415-005-0689-z · Cited by 33
Ohno, M. (2006) · Reviews in the Neurosciences · doi:10.1515/revneuro.2006.17.4.429 · Cited by 33
Guo, Z., Qiu, C., Viitanen, M. H., Fastbom, J., Winblad, B. G., & Fratiglioni, L. (2001) · Journal of Alzheimer s Disease · doi:10.3233/jad-2001-3609 · Cited by 30
Zohar, O., Cavallaro, S., D’Agata, V., & Alkon, D. L. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(03)00182-7 · Cited by 30
Kuzuya, A., Uemura, K., Kitagawa, N., Aoyagi, N., Kihara, T., Ninomiya, H., Ishiura, S., Takahashi, R., & Shimohama, S. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.21104 · Cited by 28
Extracellular release of BACE1 holoproteins from human neuronal cells
Murayama, K. S., Kametani, F., & Araki, W. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.10.015 · Cited by 26
Lindholm, T., Cullheim, S., Deckner, M., Carlstedt, T. P., & Risling, M. (2002) · Experimental Brain Research · doi:10.1007/s00221-001-0922-7 · Cited by 24
Lahiri, D., Ge, Y.-W., Rogers, J., Sambamurti, K., Greig, N., & Maloney, B. (2006) · Current Alzheimer Research · doi:10.2174/156720506779025224 · Cited by 24
Llorca, J., Rodríguez‐Rodríguez, E., Dierssen‐Sotos, T., Delgado‐Rodríguez, M., Berciano, J., & Combarros, O. (2007) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2007.00899.x · Cited by 22
Age-dependent differential expression of BACE splice variants in brain regions of tg2576 mice
Zohar, O., Pick, C. G., Cavallaro, S., Chapman, J., Katzav, A., Milman, A., & Alkon, D. L. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.10.005 · Cited by 18
Statins and the Risk of Dementia
Jick, H., Zornberg, G. L., Jick, S. S., Seshadri, S. S., & Drachman, D. A. (2001) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-200104000-00019 · Cited by 14
Parsons, R. B., & Austen, B. M. (2005) · Biochemical Society Transactions · doi:10.1042/bst0331091 · Cited by 13
Research works printed but not linked: 2
- [70]Rossner S Apelt J Schliebs R Perez-Polo JR Bigl V Neuronal and glial beta-secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology J. Neurosci. Res 2001 64 437 446 11391698
- [71]Yan R Bienkowski MJ Shuck ME Miao H Tory MC Pauley AM Brashier JR Stratman NC Mathews WR Buhl AE Carter DB Tomasselli AG Parodi LA Heinrikson RL Gurney ME Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity Nature 1999 402 533 537 10591213
Cited by
Circulating miRNAs as Biomarkers for Neurodegenerative Disorders
Grasso, M., Piscopo, P., Confaloni, A., & Denti, M. (2014) · Molecules · doi:10.3390/molecules19056891 · Cited by 208
The biosynthesis, signaling, and neurological functions of bile acids
Kiriyama, Y., & Nochi, H. (2019) · Biomolecules · doi:10.3390/biom9060232 · Cited by 204
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 ›
Are you an author, or do you see a problem with this page? Request a review
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.
