Biology subjects

Padilla-Ferrer, A.

Publications and source records attributed to Padilla-Ferrer, A..

3 recordsLinked to original sources

bioRxiv2025

Role of oligodendroglial ADAM10 in oligodendrocyte maturation, myelination and myelin maintenance

In the central nervous system, oligodendrocytes extend their processes to wrap axons to form myelin sheaths, ensuring saltatory conduction of action potentials and providing trophic support for the axon. Our previous work demonstrated that pharmacological activation of -secretase promotes myelin protection and remyelination after both ex vivo and in vivo demyelination. Based on these findings, the present study aims to investigate the role of oligodendroglial ADAM10 (OLA10; a member of the a-secretase family) in myelin development and maintenance. Using an inducible knockout mouse model for OLA10 (KOOL-A10), we demonstrated that OLA10 deficiency results in delayed maturation of OPC in primary culture, and altered myelination in primary neuron/glia co-culture. Furthermore, an induction of OLA10 deficiency in adult mice was associated with an alteration of myelin sheath thickness and long-term motor and cognitive deficit in males but not in females. Overall, our study highlights the subtle but significant role of ADAM10 expressed by oligodendrocytes in the formation and maintenance of the myelin over time, while emphasizing a sexual dimorphism that carries important relevance for current research.

neuroscience↗

bioRxiv2022

A receptor-independent signaling pathway for BDNF

In addition to its well-known receptor-mediated function in cell survival, differentiation and growth, we report that the extracellular brain-derived neurotrophic factor (BDNF) also controls the intracellular KEAP1-NRF2 cytoprotective system by a receptor-independent pathway. Extracellular BDNF can cross the cell membrane as it possesses a protein-translocation domain, also known as cell-penetrating peptide. This membrane crossing process is energy-independent, ruling out endocytosis and receptor-dependent mechanisms. Once in the cytosol, BDNF binds to KEAP1 with a nanomolar affinity, enabling nuclear translocation of NRF2 and transcription of NRF2-target genes. BDNF is thus a major regulator of NRF2 activation. A dysfunction of this BDNF-KEAP1-NRF2 pathway may be involved in most diseases where antioxidant and cytoprotective functions are altered. This novel form of communication, whereby a receptor ligand protein exerts a biological activity by crossing the cell membrane, opens new avenues for cell signaling.

cell biology↗

bioRxiv2021

RNA-Seq is not required to determine stable reference genes for qPCR normalization

Assessment of differential gene expression by qPCR is heavily influenced by the choice of reference genes. Although numerous statistical approaches have been proposed to determine the best reference genes, they can give rise to conflicting results depending on experimental conditions. Hence, recent studies propose the use of RNA-Seq to identify stable genes followed by the application of different statistical approaches to determine the best set of reference genes for qPCR data normalization. In this study, we demonstrate that the statistical approach to determine the best reference genes from randomly selected candidates is more important than the preselection of stable candidates from RNA-Seq data. Using a qPCR data normalization workflow that we have previously established; we show that qPCR data normalization using randomly chosen conventional reference genes renders the same results as stable reference genes selected from RNA-Seq data. We validated these observations in two distinct cross-sectional experimental conditions involving human iPSC derived microglial cells and mouse sciatic nerves. These results taken together show that given a robust statistical approach for reference gene selection, stable genes selected from RNA-Seq data do not offer any significant advantage over commonly used reference genes for normalizing qPCR assays.

molecular biology↗