Oliveira, Riva de PaulaBezerra, Liliane Soares de Castro2025-05-282025-05-282025-02-24BEZERRA, Liliane Soares de Castro. Caracterização das proteínas EXO-3/APE1 e XPA-1/XPA no desenvolvimento de fenótipos neurodegenerativos no Caenorhabditis elegans. Orientadora: Dra. Riva de Paula Oliveira. 2025. 66f. Dissertação (Mestrado em Bioquímica e Biologia Molecular) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2025.https://repositorio.ufrn.br/handle/123456789/63730Clinical evidence suggests that deficiencies in the nucleotide excision repair (NER) and base excision repair (BER) pathways are associated with neurodegenerative pathologies in humans, suggesting that these pathways play a key role in chronic neurodegenerative diseases. Failure of the NER pathway results in several DNA damages, such as continuous activation of poly-ADP-ribose polymerase 1 (PARP1) and decreased intracellular NAD+. However, the relationship between mitochondrial dysfunction and BER pathway deficiency is still not fully understood, as is the possible interaction with the NER pathway. The nematode Caenorhabditis elegans is a widely used model to investigate neurodegenerative diseases in developing multicellular organisms. The BER and NER pathways are well preserved in C. elegans. In this organism, the endonuclease EXO-3, homologous to APE1 of the BER pathway, and the ortholog XPA-1 of the NER pathway play key roles. exo-3 mutants present reduced progeny, increased production of reactive oxygen species (ROS) and larger mitochondrial DNA (mtDNA) deletions. On the other hand, xpa-1 mutants are sensitive to UV radiation and present deficiencies in the ubiquitin-proteasome system (UPS) and mitochondrial metabolism. Thus, we evaluated how deficiencies of EXO-3 and XPA-1 influence mitochondrial integrity and the development of neurodegenerative phenotypes in transgenic models of C. elegans. For this purpose, we analyzed exo-3 and/or xpa-1 knockdown animals from strains that emit GFP in intestinal and muscle mitochondria. In addition to observing the effect of BER and NER pathway deficiency on apoptosis, we also evaluated cholinergic neuronal integrity in animals deficient for exo-3 or xpa-1. The results indicated evidence of neurodegeneration and signs of mitochondrial dysfunction in animals deficient in both repair pathways, reinforcing the overlap of these two pathways. In addition, they are in line with what was observed in previous studies on increased mitochondrial content in exo-3;xpa-1 knockdown animals. Thus, the focus is on the development of exo-3 and xpa-1 deletion mutant animals for a better characterization of mitochondrial function and neuronal integrity. This work is expected to contribute to a better understanding of neurodegenerative diseases and the role of EXO-3, a central endonuclease in BER repair, in the emergence of neurodegenerative phenotypes and their association with mitochondrial dysfunctions.pt-BRAcesso AbertoCaenorhabditis elegansBERNERNeurodegeneraçãoDisfunção mitocondrialmasterThesisCIENCIAS BIOLOGICAS