Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.

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 neu...

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Autores principales:	Nicole Schonrock, Yazi D Ke, David Humphreys, Matthias Staufenbiel, Lars M Ittner, Thomas Preiss, Jürgen Götz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3cf4161601604376a398ba936a98b7fe
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spelling	oai:doaj.org-article:3cf4161601604376a398ba936a98b7fe2021-12-02T20:20:59ZNeuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.1932-620310.1371/journal.pone.0011070https://doaj.org/article/3cf4161601604376a398ba936a98b7fe2010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20552018/?tool=EBIhttps://doaj.org/toc/1932-6203Normal 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.Nicole SchonrockYazi D KeDavid HumphreysMatthias StaufenbielLars M IttnerThomas PreissJürgen GötzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 6, p e11070 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicole Schonrock Yazi D Ke David Humphreys Matthias Staufenbiel Lars M Ittner Thomas Preiss Jürgen Götz Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.
description	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.
format	article
author	Nicole Schonrock Yazi D Ke David Humphreys Matthias Staufenbiel Lars M Ittner Thomas Preiss Jürgen Götz
author_facet	Nicole Schonrock Yazi D Ke David Humphreys Matthias Staufenbiel Lars M Ittner Thomas Preiss Jürgen Götz
author_sort	Nicole Schonrock
title	Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.
title_short	Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.
title_full	Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.
title_fullStr	Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.
title_full_unstemmed	Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.
title_sort	neuronal microrna deregulation in response to alzheimer's disease amyloid-beta.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/3cf4161601604376a398ba936a98b7fe
work_keys_str_mv	AT nicoleschonrock neuronalmicrornaderegulationinresponsetoalzheimersdiseaseamyloidbeta AT yazidke neuronalmicrornaderegulationinresponsetoalzheimersdiseaseamyloidbeta AT davidhumphreys neuronalmicrornaderegulationinresponsetoalzheimersdiseaseamyloidbeta AT matthiasstaufenbiel neuronalmicrornaderegulationinresponsetoalzheimersdiseaseamyloidbeta AT larsmittner neuronalmicrornaderegulationinresponsetoalzheimersdiseaseamyloidbeta AT thomaspreiss neuronalmicrornaderegulationinresponsetoalzheimersdiseaseamyloidbeta AT jurgengotz neuronalmicrornaderegulationinresponsetoalzheimersdiseaseamyloidbeta
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Neuronal microRNA deregulation in response to Alzheimer's disease amyloid-beta.

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