Decoding microRNA-Protein Interaction Networks in Alzheimer's Disease: Molecular Mechanisms and Clinical Implications

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no effective disease-modifying treatments.
• MicroRNAs (miRNAs), small noncoding RNAs regulating gene expression, play crucial roles in AD pathogenesis.
• Altered miRNA levels impact critical pathways including amyloid precursor protein (APP) processing, tau phosphorylation, oxidative stress, neuroinflammation, and synaptic plasticity.

Purpose of the Study:

• To elucidate the molecular mechanisms of miRNA dysregulation in Alzheimer's disease.
• To explore the translational potential of miRNAs as diagnostic biomarkers and therapeutic targets for AD.
• To review the intricate relationship between specific miRNAs and AD-related molecular pathology.

Main Methods:

• Literature review focusing on miRNA involvement in AD molecular pathways.
• Analysis of miRNA dysregulation in relation to amyloid-beta (Aβ) production and tau hyperphosphorylation.
• Examination of the role of specific miRNAs in oxidative stress, neuroinflammation, and synaptic dysfunction in AD.

Main Results:

• Downregulation of miR-29a/b and miR-107 promotes amyloid plaque formation by increasing BACE1 activity.
• Overexpression of miR-125b and reduced miR-132/212 levels contribute to tau hyperphosphorylation via CDK5 and MAPK pathways.
• Oxidative stress-related miRNAs (e.g., miR-34a, miR-21) and pro-inflammatory miRNAs (e.g., miR-146a, miR-155) exacerbate neuronal damage and neuroinflammation.

Conclusions:

• Circulating miRNAs in biofluids show promise as minimally invasive biomarkers for early AD diagnosis and disease monitoring.
• Therapeutic strategies targeting miRNAs, such as antagomiRs or mimics, hold potential for preventing neurodegeneration.
• Understanding miRNA-protein interactions is key to developing precision-based interventions for Alzheimer's disease.