miR-519a-3p, found to regulate cellular prion protein during Alzheimer 's disease pathogenesis, as a biomarker of asymptomatic stages
Por:
Jácome, D, Cotrufo, T, Andrés-Benito, P, Lidón, L, Martí, E, Ferrer, I, del Río, JA, Gavín, R
Publicada:
1 jun 2024
Ahead of Print:
1 abr 2024
Resumen:
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 C ) 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 C expression after using of mimic technology on cell culture. In addition, RT-qPCR was performed to analyzed miR519a-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 C . 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.
Filiaciones:
Jácome, D:
Inst Bioengn Catalonia, Mol & Cellular Neurobiotechnol, Barcelona, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Barcelona, Spain
Cotrufo, T:
Inst Bioengn Catalonia, Mol & Cellular Neurobiotechnol, Barcelona, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Barcelona, Spain
Univ Barcelona, Inst Neurosci, Barcelona, Spain
Andrés-Benito, P:
Ctr Networked Biomed Res Neurodegenerat Dis CIBERN, Madrid, Barcelona, Spain
Bellvitge Inst Biomed Res IDIBELL, Neurol Dis & Neurogenet Grp, LHosp De Llobregat, Barcelona, Spain
Lidón, L:
Inst Bioengn Catalonia, Mol & Cellular Neurobiotechnol, Barcelona, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Barcelona, Spain
Univ Barcelona, Inst Neurosci, Barcelona, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBERN, Madrid, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Neurol Dept, Memory Unit, Barcelona, Spain
Martí, E:
Univ Barcelona, Inst Neurosci, Barcelona, Spain
Univ Barcelona, Dept Biomed Sci, Funct Genom Neurodegenerat Dis, Barcelona, Spain
CIBERESP Ctr Red Epidemiol & Salud Publ, Madrid, Spain
Ferrer, I:
Univ Barcelona, Inst Neurosci, Barcelona, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBERN, Madrid, Barcelona, Spain
Univ Barcelona, Dept Pathol & Expt Therapeut, Barcelona, Spain
Bellvitge Univ Hosp, Serv Pathol, Neuropathol, Lhospitalet De Llobregat, Spain
del Río, JA:
Inst Bioengn Catalonia, Mol & Cellular Neurobiotechnol, Barcelona, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Barcelona, Spain
Univ Barcelona, Inst Neurosci, Barcelona, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBERN, Madrid, Barcelona, Spain
Gavín, R:
Inst Bioengn Catalonia, Mol & Cellular Neurobiotechnol, Barcelona, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Barcelona, Spain
Univ Barcelona, Inst Neurosci, Barcelona, Spain
Ctr Networked Biomed Res Neurodegenerat Dis CIBERN, Madrid, Barcelona, Spain
hybrid, Green Submitted
|