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MicroRNA-138 promotes tau phosphorylation by targeting retinoic acid receptor alpha

Xiong Wang1, Lu Tan2, Yanjun Lu1

  • 1Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

FEBS Letters
|February 15, 2015
PubMed

Insights

MicroRNAs (miRNAs) like miR-138 are implicated in Alzheimer's disease (AD). This study reveals miR-138 promotes tau phosphorylation by targeting the retinoic acid receptor alpha (RARA)/glycogen synthase kinase-3β (GSK-3β) pathway.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) of hyperphosphorylated tau.
  • MicroRNAs (miRNAs) are increasingly recognized for their role in AD pathogenesis.

Purpose of the Study:

  • To investigate the role of miR-138, a brain-enriched miRNA elevated in AD patients, in the development of Alzheimer's disease.
  • To elucidate the molecular mechanisms by which miR-138 influences tau phosphorylation and AD pathology.

Main Methods:

  • Utilized cell line models (N2a/APP and HEK293/tau) to study miR-138 expression and function.
  • Investigated the effect of miR-138 overexpression on glycogen synthase kinase-3β (GSK-3β) activity and tau phosphorylation.
  • Identified and validated retinoic acid receptor alpha (RARA) as a direct target of miR-138.

Main Results:

  • miR-138 levels were found to be elevated in AD models.
  • Overexpression of miR-138 led to increased GSK-3β activation and tau phosphorylation.
  • Supplementation with RARA counteracted miR-138-induced GSK-3β activation and reduced tau phosphorylation.

Conclusions:

  • miR-138 promotes tau phosphorylation through the RARA/GSK-3β signaling pathway.
  • Targeting the miR-138/RARA/GSK-3β axis may offer a therapeutic strategy for Alzheimer's disease.
Keywords:
Alzheimer’s diseaseGlycogen synthase kinase-3βPhosphorylationRetinoic acid receptor alphaTaumiR-138

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