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Understanding the multifaceted role of miRNAs in Alzheimer's disease pathology
Sharanjot Kaur1, Harkomal Verma2, Sukhchain Kaur1
1Department of Microbiology, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda, Punjab, India.
Abstract:
Small non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer's disease (AD). In AD, amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of Aβ and tau is known to be associated with miRNA dysregulation. In addition, the β-site APP cleaving enzyme (BACE 1), which cleaves APP to form Aβ, is also found to be regulated by miRNAs, thus directly affecting Aβ accumulation. Growing evidences suggest that neuroinflammation can be an initial event in AD pathology, and miRNAs have been linked with the regulation of neuroinflammation. Inflammatory disorders have also been associated with AD pathology, and exosomes associated with miRNAs are known to regulate brain inflammation, suggesting for the role of systemic miRNAs in AD pathology. Several miRNAs have been related in AD, years before the clinical symptoms appear, most of which are associated with regulating the cell cycle, immune system, stress responses, cellular senescence, nerve growth factor (NGF) signaling, and synaptic regulation. Phytochemicals, especially polyphenols, alter the expression of various miRNAs by binding to miRNAs or binding to the transcriptional activators of miRNAs, thus control/alter various metabolic pathways. Awing to the sundry biological processes being regulated by miRNAs in the brain and regulation of expression of miRNAs via phytochemicals, miRNAs and the regulatory bioactive phytochemicals can serve as therapeutic agents in the treatment and management of AD.
Insights
MicroRNAs (miRNAs) are key regulators in Alzheimer's disease (AD) pathology, influencing neuroinflammation and amyloid beta plaque formation. Phytochemicals that modulate miRNA expression show therapeutic potential for AD management.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various biological processes and diseases.
- A significant number of miRNAs are expressed in the brain, playing crucial roles in synaptic functions and neurodegenerative disorders like Alzheimer's disease (AD).
- AD is characterized by amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs), with miRNA dysregulation linked to the clearance of Aβ and tau pathology.
Purpose of the Study:
- To explore the multifaceted roles of miRNAs in Alzheimer's disease pathogenesis.
- To investigate the connection between miRNA dysregulation, neuroinflammation, and key AD hallmarks like Aβ accumulation.
- To assess the potential of phytochemicals in modulating miRNA expression for therapeutic intervention in AD.
Main Methods:
- Review of existing literature on miRNA function in the brain and their association with AD.
- Analysis of miRNA involvement in regulating Aβ production via enzymes like BACE 1.
- Examination of the link between neuroinflammation, systemic miRNAs, and AD pathology.
- Investigation of phytochemicals, particularly polyphenols, and their mechanisms in altering miRNA expression.
Main Results:
- miRNA dysregulation is associated with impaired clearance of Aβ and tau in AD.
- miRNAs regulate BACE 1, directly impacting Aβ accumulation.
- Neuroinflammation, potentially an early event in AD, is regulated by miRNAs, including those delivered via exosomes.
- Specific miRNAs are linked to AD years before clinical symptoms, affecting cell cycle, immune response, and synaptic function.
- Phytochemicals can alter miRNA expression by direct binding or by affecting transcriptional activators.
Conclusions:
- miRNAs are critical regulators in AD, influencing key pathological hallmarks and neuroinflammation.
- Systemic miRNAs and exosome-mediated communication may play a role in AD pathology.
- Phytochemicals offer a promising avenue for AD therapy by modulating miRNA expression.
- miRNAs and bioactive phytochemicals represent potential therapeutic agents for AD treatment and management.
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