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APP Metabolism Regu...
APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons
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Moore, S. (author)
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Evans, L. D. B. (author)
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- Andersson, Therese (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Portelius, Erik, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Smith, J. (author)
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Dias, T. B. (author)
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Saurat, N. (author)
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McGlade, A. (author)
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Kirwan, P. (author)
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Hardy, J. (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Livesey, F. J. (author)
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 11:5, s. 689-696
- Related links:
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Abstract
Subject headings
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- Accumulation of A beta peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic A beta peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by beta-secretase and gamma-secretase inhibition, as well as gamma-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular A beta signaling to neurons.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- PLURIPOTENT STEM-CELLS
- FAMILIAL ALZHEIMERS-DISEASE
- A-BETA
- PROTEIN
- DUPLICATION
- FRAGMENT
- LOCUS
- Cell Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Moore, S.
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Evans, L. D. B.
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Andersson, There ...
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Portelius, Erik, ...
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Smith, J.
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Dias, T. B.
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show more...
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Saurat, N.
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McGlade, A.
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Kirwan, P.
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Blennow, Kaj, 19 ...
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Hardy, J.
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Zetterberg, Henr ...
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Livesey, F. J.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
- Articles in the publication
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Cell Reports
- By the university
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University of Gothenburg
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Stockholm University