<i>APP</i>and<i>BACE1</i>miRNA genetic variability has no major role in risk for Alzheimer disease

Bettens, Karolien; Brouwers, Nathalie; Engelborghs, Sebastiaan; Miegroet, Helen Van; Deyn, Peter Paul De; Theuns, Jessie; Sleegers, Kristel; Broeckhoven, Christine Van

doi:10.1002/humu.21027

Cited by 52 publications

(30 citation statements)

References 40 publications

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“…In addition to regulating BACE1, miR-29a/b are increased in the aging brain and linked to modulation of microglial activation (Fenn et al, 2013). The miR-29 cluster has been sequenced in a cohort of sporadic and familial patients and variants were found within the cluster that significantly associated with Alzheimer's disease (Bettens et al, 2009). However, this finding requires further validation in additional cohorts and the functional effects of these variants remains unclear.…”

Section: Mirnas In Neurodegenerative Disordersmentioning

confidence: 99%

Neuronal dark matter: the emerging role of microRNAs in neurodegeneration

Goodall

Heath

Bandmann

et al. 2013

Front. Cell. Neurosci.

174

117

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MicroRNAs (miRNAs) are small, abundant RNA molecules that constitute part of the cell's non-coding RNA “dark matter.” In recent years, the discovery of miRNAs has revolutionised the traditional view of gene expression and our understanding of miRNA biogenesis and function has expanded. Altered expression of miRNAs is increasingly recognized as a feature of many disease states, including neurodegeneration. Here, we review the emerging role for miRNA dysfunction in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease pathogenesis. We emphasize the complex nature of gene regulatory networks and the need for systematic studies, with larger sample cohorts than have so far been reported, to reveal the most important miRNA regulators in disease. Finally, miRNA diversity and their potential to target multiple pathways, offers novel clinical applications for miRNAs as biomarkers and therapeutic agents in neurodegenerative diseases.

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Section: Mirnas In Neurodegenerative Disordersmentioning

confidence: 99%

Neuronal dark matter: the emerging role of microRNAs in neurodegeneration

Goodall

Heath

Bandmann

et al. 2013

Front. Cell. Neurosci.

174

117

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“…Six variants in the 3′-UTR of APP and 29 variants in the 3′-UTR of BACE1 were found; few of these variants were limited to patients (Bettens et al, 2009). However, association studies with all common variants detected in the 3′-UTR of BACE-1 failed to identify an association with AD risk.…”

Section: Mirnas In Neurodegenerative Disordersmentioning

confidence: 99%

MicroRNAs in neurodegenerative diseases and their therapeutic potential

Junn¹,

Mouradian²

2012

Pharmacology & Therapeutics

193

126

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MicroRNAs (miRNAs) are abundant, endogenous, short, noncoding RNAs that act as important post-transcriptional regulators of gene expression by base-pairing with their target mRNA. During the last decade, substantial knowledge has accumulated regarding the biogenesis of miRNAs, their molecular mechanisms and functional roles in a variety of cellular contexts. Altered expression of certain miRNA molecules in the brains of patients with neurodegenerative diseases such as Alzheimer and Parkinson suggests that miRNAs could have a crucial regulatory role in these disorders. Polymorphisms in miRNA target sites may also constitute an important determinant of disease risk. Additionally, emerging evidence points to specific miRNAs targeting and regulating the expression of particular proteins that are key to disease pathogenesis. Considering that the amount of these proteins in susceptible neuronal populations appears to be critical to neurodegeneration, miRNA-mediated regulation represents a new target of significant therapeutic prospects. In this review, the implications of miRNAs in several neurodegenerative disorders and their potential as therapeutic interventions are discussed.

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“…This suggests that miR-29a/b is capable of significantly modulating BACE1 and consequently the production of the toxic Aβ peptide. Currently there is no evidence to indicate that genetic polymorphisms in miR-29a/b or the 3′ UTRs of APP or BACE1 contribute to AD, suggesting that the miR-29a/b - BACE1 interaction may not be causative in familial forms of AD 27 .…”

Section: Mirnas Alter Protein Accumulationmentioning

confidence: 99%