Unravelling BRI2 role in neuronal differentiation

• Autor(a) principal: Monteiro, Bruno André Catarino Silva
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/35958
• topic: Neurogenesis; Neuronal differentiation; Neuritogenesis; BRI2; SH-SY5Y; Proteolytic processing

Adult neurogenesis describes the process in which new neurons are formed from neuronal stem cells past the early developmental period. In humans, adult neurogenesis was thought to occur exclusively within the subventricular zone and subgranular zone niches, however, novel neurogenic niches, such as the substancia nigra, cortex and hypothalamus, have been proposed. This process requires the migration of committed proliferating neuronal precursors into existing neuronal circuits, where they differentiate into mature neurons and are synaptically integrated. Abnormalities in any of these stages impair neurogenesis and could compromise brain function. In fact, impaired neurogenesis seems to be a common hallmark in several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Hence, researchers are trying to find new pro-neurogenic therapeutic approaches to increase basal levels of neurogenesis in patients with neurodegenerative diseases. These include lifestyle interventions, pharmacological strategies, gene therapies, stem cell therapies and glia-to-neuron reprogramming. Nonetheless, currently there is not an available therapy for neurodegenerative diseases that targets neurogenesis. BRI2 is a ubiquitous type II transmembrane protein which is highly expressed in the central nervous system, namely cortex and hippocampus. This protein undergoes regulated intramembrane proteolysis which results in the shedding of several short peptides. The precise physiological function of BRI2 and its proteolytic fragments remains elusive, however, a putative role in neuronal differentiation has recently been proposed by our group. Indeed, BRI2 expression and processing were found to be substantially increased during the neuronal maturation process. Therefore, promotion of neuronal differentiation through a BRI2-dependent therapeutic strategy might prove to be a useful method to increase neurogenic activity. Herein, we investigated the effect of a recombinant BRI2 peptide fragment on the differentiation phenotype of the neuroblastoma-like SH-SY5Y cell line. The results obtained indicate that the produced recombinant peptide at doses and times incubated does not have an effect in the SH-SY5Y differentiation, as no significant differences were observed when compared to the control. Nevertheless, given the previously established relevant role of BRI2 and its proteolytic processing in neuronal maturation, more research should be conducted before ruling out BRI2 as a modulator of neuronal differentiation.