Soluble beta-amyloid peptides, but not insoluble fibrils, have specific effect on neuronal MicroRNA expression

Jing Jing Li, Georgia Dolios, Rong Wang, Francesca-Fang Liao

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Recent studies indicate that soluble b-amyloid (sAβ) oligomers, rather than their fibrillar aggregates, contribute to the pathogenesis of Alzheimer's disease (AD), though the mechanisms of their neurotoxicity are still elusive. Here, we demonstrate that sAb derived from 7PA2 cells exert a much stronger effect on the regulation of a set of functionally validated microRNAs (miRNAs) in primary cultured neurons than the synthetic insoluble Aβ fibrils (fAβ). Synthetic sAβ peptides at a higher concentration present comparable effect on these miRNAs in our neuronal model. Further, the sAβ-induced miR-134, miR-145 and miR-210 expressions are fully reversed by two selective N-methyl-d-aspartate (NMDA) receptor inhibitors, but are neither reversed by insulin nor by forskolin, suggesting an NMDA receptor-dependent, rather than PI3K/AKT or PKA/CREB signaling dependent regulatory mechanism. In addition, the repression of miR-107 expression by the sAβ containing 7PA2 CM is likely involved multiple mechanisms and multiple players including NMDA receptor, N-terminally truncated Aβ and reactive oxygen species (ROS).

Original languageEnglish (US)
Article numbere90770
JournalPLoS ONE
Volume9
Issue number3
DOIs
StatePublished - Mar 4 2014

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Amyloid beta-Peptides
amyloid
MicroRNAs
microRNA
Amyloid
aspartic acid
peptides
receptors
forskolin
neurotoxicity
phosphatidylinositol 3-kinase
protein aggregates
Colforsin
Alzheimer disease
Phosphatidylinositol 3-Kinases
Oligomers
Neurons
reactive oxygen species
Reactive Oxygen Species
Alzheimer Disease

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Soluble beta-amyloid peptides, but not insoluble fibrils, have specific effect on neuronal MicroRNA expression. / Li, Jing Jing; Dolios, Georgia; Wang, Rong; Liao, Francesca-Fang.

In: PLoS ONE, Vol. 9, No. 3, e90770, 04.03.2014.

Research output: Contribution to journalArticle

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