Banca de DEFESA: LILIANE SOARES DE CASTRO BEZERRA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : LILIANE SOARES DE CASTRO BEZERRA
DATE: 24/02/2025
TIME: 14:00
LOCAL: Videoconferência - Link para acesso: https://meet.google.com/txz-pbjm-kgi
TITLE:

Characterization of EXO-3/APE1 and XPA-1/XPA proteins in development of neurodegenerative phenotypes in Caenorhabditis elegans

KEY WORDS:

BER, NER, APE-1, XPA, Mitophagy, Neurodegeneration, Caenorhabditis elegans

 

PAGES: 65
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

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.

 

COMMITTEE MEMBERS:
Interna - 1837354 - JULLIANE TAMARA ARAUJO DE MELO CAMPOS
Externa ao Programa - 1251018 - RIVA DE PAULA OLIVEIRA - UFRNExterno à Instituição - EVANDRO ARAUJO DE SOUZA - USP