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Phenotypic Screenin...
Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease.
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Brownjohn, Philip W (author)
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Smith, James (author)
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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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Serneels, Lutgarde (author)
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- Kvartsberg, Hlin, 1987 (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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De Strooper, Bart (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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- 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, Frederick J (author)
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
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In: Stem cell reports. - : Elsevier BV. - 2213-6711. ; 8:4, s. 870-882
- Related links:
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http://www.cell.com/...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP) processing and the accumulation of APP-derived amyloid β (Aβ) peptides are key processes in Alzheimer's disease (AD). We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer Disease
- drug therapy
- metabolism
- pathology
- Amyloid Precursor Protein Secretases
- metabolism
- Amyloid beta-Protein Precursor
- metabolism
- Anthelmintics
- chemistry
- pharmacology
- Cells
- Cultured
- Down Syndrome
- metabolism
- pathology
- Drug Discovery
- methods
- Humans
- Induced Pluripotent Stem Cells
- metabolism
- pathology
- Ivermectin
- analogs & derivatives
- chemistry
- pharmacology
- Neurogenesis
- Neurons
- drug effects
- metabolism
- pathology
- Phenotype
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Brownjohn, Phili ...
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Smith, James
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Portelius, Erik, ...
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Serneels, Lutgar ...
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Kvartsberg, Hlin ...
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De Strooper, Bar ...
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Blennow, Kaj, 19 ...
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Zetterberg, Henr ...
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Livesey, Frederi ...
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- 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 Neurosciences
- Articles in the publication
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Stem cell report ...
- By the university
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University of Gothenburg