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Involvement of transposable elements in Alzheimer's disease pathogenesis.
R N Mustafin1, E K Khusnutdinova2
1Bashkir State Medical University, Ufa, Russia.
Vavilovskii Zhurnal Genetiki I Selektsii
|April 29, 2024
Summary
Transposons, mobile genetic elements, are implicated in Alzheimer's disease pathogenesis. Their dysregulation, particularly LINE retroelements, influences microRNA expression, potentially linking aging, cancer, and Alzheimer's disease through altered epigenetic regulation.
Area of Science:
- Genetics and Epigenetics
- Neuroscience
- Molecular Biology
Background:
- Alzheimer's disease (AD) prevalence increases with age, suggesting shared aging mechanisms.
- Transposons, or mobile genetic elements, act as drivers of epigenetic regulation.
- MicroRNAs (miRNAs) are implicated in AD pathogenesis, but complex genetic associations remain challenging to fully explain.
Purpose of the Study:
- To investigate the role of transposon-derived microRNAs in Alzheimer's disease.
- To explore potential common pathogenetic mechanisms linking aging, cancer, and AD through transposon dysregulation.
Main Methods:
- Literature analysis of scientific studies and the MDTE database.
- Identification and characterization of microRNAs derived from various transposon classes (LINE, SINE, HERV, DNA transposons).
- Analysis of specific expression changes of these microRNAs in Alzheimer's disease and their correlation with aging and cancer.
Main Results:
- Identified 28 transposon-derived miRNAs with altered expression in Alzheimer's disease (17 decreased, 11 increased).
- Found that 13 of these miRNAs also exhibit expression changes during aging and cancer development.
- Observed that most dysregulated miRNAs originate from LINE retroelements, which are pathologically activated in AD, aging, and cancer.
Conclusions:
- Transposon dysregulation, particularly of LINE retroelements, may be a fundamental mechanism driving Alzheimer's disease.
- Common pathogenetic pathways involving transposon-mediated epigenetic regulation might link aging, cancer, and Alzheimer's disease.
- Targeting transposon activity could offer novel therapeutic and preventive strategies for Alzheimer's disease.
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