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Cited by 211Alzheimer's disease research and treatmentsMicroRNA in disease regulationNeuroinflammation and Neurodegeneration Mechanisms

Neuronal MicroRNA Deregulation in Response to Alzheimer's Disease Amyloid-β

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Schonrock, Nicole, Ke, Yazi D., Humphreys, David, Staufenbiel, Matthias, Ittner, Lars M., Preiss, Thomas, Götz, Jürgen·2010·PLoS ONE
DOI 10.1371/journal.pone.0011070PMC PMC2884018
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Abstract

Normal brain development and function depends on microRNA (miRNA) networks to fine tune the balance between the transcriptome and proteome of the cell. These small non-coding RNA regulators are highly enriched in brain where they play key roles in neuronal development, plasticity and disease. In neurodegenerative disorders such as Alzheimer's disease (AD), brain miRNA profiles are altered; thus miRNA dysfunction could be both a cause and a consequence of disease. Our study dissects the complexity of human AD pathology, and addresses the hypothesis that amyloid-beta (Abeta) itself, a known causative factor of AD, causes neuronal miRNA deregulation, which could contribute to the pathomechanisms of AD. We used sensitive TaqMan low density miRNA arrays (TLDA) on murine primary hippocampal cultures to show that about half of all miRNAs tested were down-regulated in response to Abeta peptides. Time-course assays of neuronal Abeta treatments show that Abeta is in fact a powerful regulator of miRNA levels as the response of certain mature miRNAs is extremely rapid. Bioinformatic analysis predicts that the deregulated miRNAs are likely to affect target genes present in prominent neuronal pathways known to be disrupted in AD. Remarkably, we also found that the miRNA deregulation in hippocampal cultures was paralleled in vivo by a deregulation in the hippocampus of Abeta42-depositing APP23 mice, at the onset of Abeta plaque formation. In addition, the miRNA deregulation in hippocampal cultures and APP23 hippocampus overlaps with those obtained in human AD studies. Taken together, our findings suggest that neuronal miRNA deregulation in response to an insult by Abeta may be an important factor contributing to the cascade of events leading to AD.

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  • miR-21 is associated with regulation of toxicity mediated by Aβ oligomers, both in vitro and in vivo.

    “Among these, miR-125b is associated with Tau phosphorylation [30], miR-124 with neuronal function and APP processing [25,31], and miR-21 to the regulation of toxicity mediated by Aβ oligomers, both in vitro and in vivo [32].”

    From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [32]

    The Results section on the APP23 mouse model reports miR-21 down-regulation alongside miRNA changes in Aβ-treated neuronal cultures, supporting an in vivo and in vitro association with Aβ exposure (page unavailable). It does not show that miR-21 regulates Aβ-oligomer-mediated toxicity; the Results section on cultured neurons reports no observed toxicity or cell death under the exposure conditions used. (LLM, conf=0.88)

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Authors
Schonrock, N., Ke, Y. D., Humphreys, D., Staufenbiel, M., Ittner, L. M., Preiss, T., & Götz, J.
Affiliations
  • The University of Sydney (AU)
  • Victor Chang Cardiac Research Institute (AU)
  • Novartis (Switzerland) (CH)
Corresponding author
Götz, Jürgen
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-06-11
Volume
5
Issue
6
Pages
e11070
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0011070
PMC
PMC2884018
OpenAlex
W1993576110
Cited by
211
References
8
Citations by year
2026: 3 · 2025: 3 · 2024: 16 · 2023: 6 · 2022: 10 · 2021: 5 · 2020: 17 · 2019: 13 · 2018: 9 · 2017: 12 · 2016: 10 · 2015: 18 · 2014: 22 · 2013: 19 · 2012: 26
FWCI
14.52
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • ANU Open Research (Australian National University) (submittedVersion, cc-by)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by)
Funders
  • GlaxoSmithKline
  • University of Sydney
  • Medical Research Council
  • Australian Research Council
  • National Health and Medical Research Council
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid-beta, microRNA dysregulation, hippocampus, APP23 mice, amyloid plaques, miRNA target genes, neurodegeneration, non-coding RNA regulation
MeSH terms
Alzheimer Disease, Animals, Immunohistochemistry, Mice, Inbred C57BL, Mice, Transgenic, RNA, Messenger, Polymerase Chain Reaction, Amyloid beta-Peptides, Mice

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