Document details

Integration of omics to explore novel disease pathways in Down syndrome neurodegeneration focusing on integrated stress response

Author(s): Barros-Santos, Beatriz ; Campos-Marques, Carlos ; Salvador, Andreia Filipa Ferreira ; Silva, Joana Margarida Gonçalves Mota

Date: 2025

Persistent ID: https://hdl.handle.net/1822/95513

Origin: RepositóriUM - Universidade do Minho

Project/scholarship: info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50026%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50026%2F2020/PT;

Subject(s): ISR pathway; RNA metabolism; Stress Granules; Neurodegeneration; Down syndrome; Biomarkers


Description

Down Syndrome is characterized by the trisomy of chromosome 21, leading to widespread molecular and neurological alterations, including early-onset Alzheimer's disease. Emerging evidence highlights the role of RNA metabolism, RNA-binding proteins, and stress granules in these processes. The integrated stress response, a key regulator of translation and protein homeostasis, may be particularly disrupted in DS due to the overexpression of genes involved in the balance between protein degradation and RNA transcription. However, its impact on neurodegeneration in DS remains poorly understood. This project aims to integrate transcriptomic and proteomic data from human and animal models with Down Syndrome to dissect the interplay between integrated stress response, RNA-binding proteins, and stress granule dynamics. By identifying key molecular disruptions in RNA homeostasis and protein synthesis, we aim to investigate novel disease-driving mechanisms that can be conserved among species. These insights will likely help to establish ISR as a potential therapeutic target, advancing our understanding of DS-related neurodegenerative pathways that could be behind the age-related neurodegeneration observed in DS.

This work has been funded by National funds through the Foundation for Science and Technology (FCT) - projects UIDB/50026/2020 and UIDP/50026/2020. JMS was supported by national funds through FCT Contract for Scientific Employment (2021.00204.CEECCIND). CCM was supported by national funds through FCT PhD support fellowships program.

info:eu-repo/semantics/publishedVersion

Document Type Journal article
Language English
Contributor(s) Universidade do Minho
CC Licence
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