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MEG3 activates necr...
MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer's disease.
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Balusu, Sriram (author)
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Horré, Katrien (author)
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Thrupp, Nicola (author)
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Craessaerts, Katleen (author)
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Snellinx, An (author)
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Serneels, Lutgarde (author)
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T'Syen, Dries (author)
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Chrysidou, Iordana (author)
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Arranz, Amaia M (author)
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Sierksma, Annerieke (author)
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- Simrén, Joel, 1996 (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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- Karikari, Thomas (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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Chen, Wei-Ting (author)
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Thal, Dietmar Rudolf (author)
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Salta, Evgenia (author)
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Fiers, Mark (author)
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De Strooper, Bart (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Science (New York, N.Y.). - 1095-9203. ; 381:6663, s. 1176-1182
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Abstract
Subject headings
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- Neuronal cell loss is a defining feature of Alzheimer's disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model of AD. Only human neurons displayed tangles, Gallyas silver staining, granulovacuolar neurodegeneration (GVD), phosphorylated tau blood biomarkers, and considerable neuronal cell loss. The long noncoding RNA MEG3 was strongly up-regulated in human neurons. This neuron-specific long noncoding RNA is also up-regulated in AD patients. MEG3 expression alone was sufficient to induce necroptosis in human neurons in vitro. Down-regulation of MEG3 and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons. This model suggests potential therapeutic approaches for AD and reveals a human-specific vulnerability to AD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Animals
- Humans
- Mice
- Alzheimer Disease
- pathology
- Heterografts
- Necroptosis
- genetics
- Neurons
- pathology
- RNA
- Long Noncoding
- genetics
- metabolism
- Protein Kinases
- genetics
- Receptor-Interacting Protein Serine-Threonine Kinases
- genetics
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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Balusu, Sriram
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Horré, Katrien
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Thrupp, Nicola
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Craessaerts, Kat ...
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Snellinx, An
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Serneels, Lutgar ...
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show more...
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T'Syen, Dries
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Chrysidou, Iorda ...
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Arranz, Amaia M
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Sierksma, Anneri ...
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Simrén, Joel, 19 ...
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Karikari, Thomas
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Zetterberg, Henr ...
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Chen, Wei-Ting
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Thal, Dietmar Ru ...
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Salta, Evgenia
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Fiers, Mark
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De Strooper, Bar ...
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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 Neurosciences
- Articles in the publication
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Science (New Yor ...
- By the university
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University of Gothenburg