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Mesenchymal Stem Cells from Familial Alzheimer's Patients Express MicroRNA Differently
Lory J Rochín-Hernández1, Lory S Rochín-Hernández2, Mayte L Padilla-Cristerna1
1Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Instituto Politécnico Nacional 2508, Ciudad de México 07360, Mexico.
Abstract:
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the predominant form of dementia globally. No reliable diagnostic, predictive techniques, or curative interventions are available. MicroRNAs (miRNAs) are vital to controlling gene expression, making them valuable biomarkers for diagnosis and prognosis. This study examines the transcriptome of olfactory ecto-mesenchymal stem cells (MSCs) derived from individuals with the PSEN1(A431E) mutation (Jalisco mutation). The aim is to determine whether this mutation affects the transcriptome and expression profile of miRNAs and their target genes at different stages of asymptomatic, presymptomatic, and symptomatic conditions. Expression microarrays compare the MSCs from mutation carriers with those from healthy donors. The results indicate a distinct variation in the expression of miRNAs and mRNAs among different symptomatologic groups and between individuals with the mutation. Using bioinformatics tools allows us to identify target genes for miRNAs, which in turn affect various biological processes and pathways. These include the cell cycle, senescence, transcription, and pathways involved in regulating the pluripotency of stem cells. These processes are closely linked to inter- and intracellular communication, vital for cellular functioning. These findings can enhance our comprehension and monitoring of the disease's physiological processes, identify new disorder indicators, and develop innovative treatments and diagnostic tools for preventing or treating AD.
Insights
This study reveals distinct microRNA (miRNA) and mRNA expression changes in olfactory stem cells from individuals with the PSEN1 mutation, offering new insights into Alzheimer's disease (AD) progression and potential biomarkers.
Area of Science:
- Neuroscience
- Genetics
- Stem Cell Biology
Background:
- Alzheimer's disease (AD) is a leading cause of dementia with no cure.
- MicroRNAs (miRNAs) are crucial gene regulators and potential biomarkers.
- The PSEN1(A431E) mutation, also known as the Jalisco mutation, is linked to familial AD.
Purpose of the Study:
- To investigate the impact of the PSEN1(A431E) mutation on the transcriptome of olfactory ecto-mesenchymal stem cells (MSCs).
- To analyze miRNA and mRNA expression profiles across different disease stages (asymptomatic, presymptomatic, symptomatic).
- To identify miRNA targets and affected biological pathways relevant to AD.
Main Methods:
- Transcriptome analysis using expression microarrays on MSCs from mutation carriers and healthy donors.
- Bioinformatic analysis to identify differentially expressed miRNAs and mRNAs.
- Target gene prediction for identified miRNAs.
Main Results:
- Significant variations in miRNA and mRNA expression were observed between mutation carriers and controls, and across different symptomatologic groups.
- Bioinformatics identified specific miRNA targets involved in cell cycle, senescence, and pluripotency regulation.
- These targets are linked to crucial cellular communication pathways.
Conclusions:
- The PSEN1(A431E) mutation alters the transcriptome and miRNA expression profile in olfactory MSCs.
- These findings enhance understanding of AD's physiological mechanisms.
- This research may lead to novel diagnostic indicators and therapeutic strategies for Alzheimer's disease.
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