Study of the influence of signaling Toll-Like Receptors (TLRs) and the gene MyD88 on olfactry epithelium neuronal regeneration

Abstract

The Nervous System (NS) is essential for animal interaction with theenvironment. However, lesions in the mammalian CNS are usually irreversible due to its limited regenerative capacity. The regenerative process that follows injury recruits cells of the immune system, which is also the case for brain lesions. Immune cells mediate the innate immune response through activation of receptors that detect molecular Pathogen-Associated Molecular Patterns (PAMPs). Among these receptors, the Toll-Like Receptor (TLR) family engages major defense mechanism upon PAMPs detection. TLRs are associated with intracellular adapter molecules that trigger gene expression of inflammatory signals for the neutralization and elimination of pathogens, as well as the restoration and modification of the injured tissue. Our studies indicate that TLR signaling components slow the neuroregeneration of the murine Olfactory Epithelium (OE). For a better understanding of the mechanisms involved, we will characterize the gene expression profile related to better nerve regeneration. In addition, we will analyze the impact of strategies for TLRs activation or interference through bone marrow chimerism, the use of peptide agonists or inhibitors and also by means of antiinflammatory therapies, which can help define if the use of these compounds is applicable in case of OE injury. (AU)