Title: Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration
Authors: Hébert, Sébastien
Papadopoulou, Aikaterini
Smith, Pascal
Galas, Marie-Christine
Planel, Emmanuel
Silahtaroglu, Asli N
Sergeant, Nicolas
Buée, Luc
De Strooper, Bart # ×
Issue Date: Oct-2010
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:19 issue:20 pages:3959-3969
Abstract: The type III RNase Dicer is responsible for the maturation and function of microRNA (miRNA) molecules in the cell. It is now well documented that Dicer and the fine-tuning of the miRNA gene network are important for neuronal integrity. However, the underlying mechanisms involved in neuronal death, particularly in the adult brain, remain poorly defined. Here, we show that absence of Dicer in the adult forebrain is accompanied by a mixed neurodegenerative phenotype. While neuronal loss is observed in the hippocampus, cellular shrinkage is predominant in the cortex. Interestingly, neuronal degeneration coincides with the hyperphosphorylation of endogenous tau at several epitopes previously associated with neurofibrillary pathology. Transcriptome analysis of enzymes involved in tau phosphorylation identified ERK1 as one of the candidate kinases responsible for this event in vivo. We further demonstrate that miRNAs belonging to the miR-15 family are potent regulators of ERK1 expression in mouse neuronal cells and co-expressed with ERK1/2 in vivo. Last, we show that miR-15a is specifically downregulated in Alzheimer's disease brain. In sum, these results support the hypothesis that changes in the miRNA network may contribute to a neurodegenerative phenotype by affecting tau phosphorylation.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for the Research of Neurodegenerative Diseases
× corresponding author
# (joint) last author

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