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Browsing by Author "Carlos, Beatriz de Almeida"

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  • The role of miRNA-9 and miRNA-29 and their specific strands (-5p and -3p) in Alzheimer’s disease
    Publication . Carlos, Beatriz de Almeida; Cruz, Carla Patrícia Alves Freire Madeira da; Riscado, Micaela Sofia Ribeiro; Sousa, Fani Pereira de
    MicroRNAs (miRNAs) are small non-coding, single-stranded RNA molecules, typically with 20-25 nucleotides in length. They play a crucial role in modulating several biological processes by regulating gene expression at the post-transcriptional level. Due to their biological role, their application is being evaluated in the context of diagnosis and treatment of neurodegenerative diseases, particularly Alzheimer's disease (AD), as biomarkers or potential therapeutic agents. AD, classified as the most common form of dementia, is an irreversible neurodegenerative disease with a high prevalence in elderly people. This disease is characterized by the accumulation of amyloid ß (Aß) peptides and hyperphosphorylated Tau protein. Several studies have demonstrated the promising effect of miRNAs for silencing the dysregulated proteins involved in the amyloid pathway, which are responsible for AD progression. With this in mind, this work aims to study the effect of miRNA-9, -29b, their specific strands (-5p and- 3p), and as well their precursor forms (pre-miRNA-9-1 and pre-miRNA-29b-1) on the proteins related with AD, such as APP, BACE1 and PS1. To proceed with this evaluation, the different forms of miRNA were encapsulated in chitosan nanoparticles and delivered in the N2a695 cell line, an AD in vitro model. After extraction of the total RNA from the cells, the mRNA levels of the target proteins were evaluated by Real-Time Polymerase Chain Reaction (qPCR). This study demonstrated a potential silencing effect by miRNA-9 on the mRNA levels of PS1 and BACE1, with pre-miRNA-9-1 via miRNA-9-1-5p being the most promising, as it induced the silencing of BACE1 mRNA in almost 50%. In conclusion, understanding how miRNAs can silence proteins involved in the amyloid pathway is crucial because these small RNAs have the potential as new therapeutic tools for treating or controlling AD progression.
    2024-11-13Master thesis Open access Show more