articleScienceSep 14, 2023HYBRID OA

MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease

SBSriram BalusuKHKatrien HorréNTNicola ThruppKCKatleen CraessaertsASAn Snellinx

VIB-KU Leuven Center for Brain & Disease Research · Ikerbasque · +10 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

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…

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211
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48.70
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100%
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70
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Authors

18

Topics & keywords

Topics
Keywords
  • Necroptosis
  • Neurodegeneration
  • Biology
  • Cell biology
  • Kinase
  • Programmed cell death
  • Neuron
  • Human brain
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