miR-519a-3p, found to regulate cellular prion protein during Alzheimer's disease pathogenesis, as a biomarker of asymptomatic stages
Jácome, Dayaneth (Universitat de Barcelona)
Cotrufo, Tiziana (Universitat de Barcelona)
Andrés-Benito, P. (Hospital Universitari de Bellvitge)
Lidón Gil, Laia (Institut de Recerca Sant Pau)
Martí, Eulàlia (Universitat de Barcelona)
Ferrer, Isidro (Hospital Universitari de Bellvitge)
Rio, Jose Antonio del (Universitat de Barcelona)
Gavín, Rosalina (Universitat de Barcelona)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Clinical relevance of miRNAs as biomarkers is growing due to their stability and detection in biofluids. In this, diagnosis at asymptomatic stages of Alzheimer's disease (AD) remains a challenge since it can only be made at autopsy according to Braak NFT staging. Achieving the objective of detecting AD at early stages would allow possible therapies to be addressed before the onset of cognitive impairment. Many studies have determined that the expression pattern of some miRNAs is dysregulated in AD patients, but to date, none has been correlated with downregulated expression of cellular prion protein (PrP) during disease progression. That is why, by means of cross studies of miRNAs up-regulated in AD with in silico identification of potential miRNAs-binding to 3'UTR of human PRNP gene, we selected miR-519a-3p for our study. Then, in vitro experiments were carried out in two ways. First, we validated miR-519a-3p target on 3'UTR-PRNP, and second, we analyzed the levels of PrP expression after using of mimic technology on cell culture. In addition, RT-qPCR was performed to analyzed miR-519a-3p expression in human cerebral samples of AD at different stages of disease evolution. Additionally, samples of other neurodegenerative diseases such as other non-AD tauopathies and several synucleinopathies were included in the study. Our results showed that miR-519a-3p overlaps with PRNP 3'UTR in vitro and promotes downregulation of PrP. Moreover, miR-519a-3p was found to be up-regulated exclusively in AD samples from stage I to VI, suggesting its potential use as a novel label of preclinical stages of the disease.
Ajuts:	Agencia Estatal de Investigación PDC2022-133268-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00453
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Biomarker ; Cellular prion protein ; MicroRNAs
Publicat a:	Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1870 Núm. 5 (june 2024) , p. 167187, ISSN 1879-260X

DOI: 10.1016/j.bbadis.2024.167187
PMID: 38653354

8 p, 1.5 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
Articles > Articles de recerca
Articles > Articles publicats