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Published on: December 26, 2016
MicroRNAs Modulate the Pathogenesis of Alzheimer's Disease: An In Silico Analysis in the Human Brain
Agnese Gugliandolo1, Luigi Chiricosta1, Virginia Boccardi2
1IRCCS Centro Neurolesi "Bonino Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Abstract:
MicroRNAs (miRNAs) are small RNAs involved in the post-transcriptional regulation of their target genes, causing a decrease in protein translation from the mRNA. Different miRNAs are found in the nervous system, where they are involved in its physiological functions, but altered miRNAs expression was also reported in neurodegenerative disorders, including Alzheimer's disease (AD). AD is characterized by memory loss, cognitive function abnormalities, and various neuropsychiatric disturbances. AD hallmarks are amyloid β (Aβ) aggregates, called senile plaques, and neurofibrillary tangles (NFTs) formed by hyperphosphorylated Tau protein. In this study, we performed an in silico analysis to evaluate altered patterns of miRNAs expression in the brains of AD patients compared to healthy subjects. We found 12 miRNAs that were differentially expressed in AD compared to healthy individuals. These miRNAs have target genes involved in AD pathogenesis. In particular, some miRNAs influence Aβ production, having as target secretase and amyloid precursor protein (APP). Some miRNAs were reported to be involved in nervous system functions, and their alteration can cause neuronal dysfunction.
Insights
Altered microRNA (miRNA) expression in the brain is linked to Alzheimer's disease (AD). This study identified 12 specific miRNAs affecting key AD pathways like amyloid precursor protein (APP) production.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression post-transcriptionally.
- Altered miRNA expression is implicated in neurodegenerative disorders, notably Alzheimer's disease (AD).
- AD is pathologically defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs).
Purpose of the Study:
- To investigate differential miRNA expression patterns in the brains of AD patients versus healthy controls using in silico analysis.
- To identify specific miRNAs and their target genes involved in Alzheimer's disease pathogenesis.
Main Methods:
- In silico analysis of miRNA expression profiles.
- Comparison of miRNA expression between Alzheimer's disease brains and healthy brain samples.
Main Results:
- Identified 12 differentially expressed miRNAs in Alzheimer's disease brains.
- These miRNAs target genes crucial for AD pathogenesis, including those involved in amyloid precursor protein (APP) processing and Aβ production.
- Some identified miRNAs are known to regulate nervous system functions, and their dysregulation may lead to neuronal dysfunction.
Conclusions:
- Specific miRNA expression alterations are associated with Alzheimer's disease.
- These miRNAs play a role in key pathological mechanisms of AD, such as Aβ production.
- Dysregulated miRNAs represent potential therapeutic targets for Alzheimer's disease.
