2026-06-27T12:36:19Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/66352025-09-15T14:45:10Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Díez Hernando, Sergio author Mejías, Andrés author Sánchez, Diego author Gutiérrez Pozo, Gabriel author Ganfornina, María D. 2023-06-16T15:25:20Z 2023-06-16T15:25:20Z 2020 1932-6203 10.1371/journal.pone.0234857 https://hdl.handle.net/20.500.14352/6635 https://doi.org/10.1371/journal.pone.0234857 The Lipocalin Apolipoprotein D (ApoD) is one of the few genes consistently overexpressed in the aging brain, and in most neurodegenerative and psychiatric diseases. Its functions include metabolism regulation, myelin management, neuroprotection, and longevity regulation. Knowledge of endogenous regulatory mechanisms controlling brain disease-triggered ApoD expression is relevant if we want to boost pharmacologically its neuroprotecting potential. In addition to classical transcriptional control, Lipocalins have a remarkable variability in mRNA 5’UTR-dependent translation efficiency. Using bioinformatic analyses, we uncover strong selective pressures preserving ApoD 5’UTR properties, indicating unexpected functional conservation. PCR amplifications demonstrate the production of five 5’UTR variants (A-E) in mouse ApoD, with diverse expression levels across tissues and developmental stages. Importantly, Variant E is specifically expressed in the oxidative stress-challenged brain. Predictive analyses of 5’UTR secondary structures and enrichment in elements restraining translation, point to Variant E as a tight regulator of ApoD expression. We find two genomic regions conserved in human and mouse ApoD: a canonical (α) promoter region and a previously unknown region upstream of Variant E that could function as an alternative mouse promoter (β). Luciferase assays demonstrate that both α and β promoter regions can drive expression in cultured mouse astrocytes, and that Promoter β activity responds proportionally to incremental doses of the oxidative stress generator Paraquat. We postulate that Promoter β works in association with Variant E 5’UTR as a regulatory tandem that organizes ApoD gene expression in the nervous system in response to oxidative stress, the most common factor in aging and neurodegeneration. eng Atribución 3.0 España Control of the neuroprotective Lipocalin Apolipoprotein D expression by alternative promoter regions and differentially expressed mRNA 5’ UTR variants journal article URL https://docta.ucm.es/bitstreams/4dd566e2-11cd-40cf-9ae7-3c901ae5a4cd/download File MD5 cc9054c6e95700a6131669c9680746bb 3801504 application/pdf Diez-Hernando, Sergio et al. . 2020. Control of the neuroprotective Lipocalin.....pdf URL https://docta.ucm.es/bitstreams/c6447d6b-2ccb-4990-8a6b-3a4c229d13d8/download File MD5 da1e2e019259f646bd52135b835ca7fa 72352 text/plain Diez-Hernando, Sergio et al. . 2020. Control of the neuroprotective Lipocalin.....pdf.txt