Oliveira, Riva de PaulaViana, Aian dos Santos2024-08-202024-08-202024-08-08VIANA, Aian dos Santos. Comparação do efeito da deficiência dos genes csb-1, xpa-1 e xpc-1 sobre a integridade dos neurônios colinérgicos no Caenorhabditis elegans. 2024. 31 f. Trabalho de Conclusão de Curso (Graduação em Biomedicina) – Universidade Federal do Rio Grande do Norte, Natal, 2024.https://repositorio.ufrn.br/handle/123456789/59448Bulky DNA damage, especially that caused by UV, is repaired by the nucleotide excision repair (NER) pathway. The NER pathway is divided into two sub-pathways, GG-NER, related to correcting damage to the genome, and TC-NER, responsible for correcting errors found during DNA replication. Effects on the function of these pathways lead to a series of diseases such as xeroderma pigmentosum and crokaine syndrome, which have certain neurological and neurodegenerative phenotypes. Recent studies indicate that NER deficiency causes mitochondrial dysfunction related to the manifestation of the neurodegenerative phenotype. Although the involvement of XPA and CSB in the neurodegeneration process is already known, the comparative contribution of these genes to the integrity of cholinergic projections has not yet been thoroughly studied. This study aims to compare the neurodegenerative effect of inhibiting the function of the csb-1, xpc-1 and xpa-1 genes in the model organism Caenorhabditis elegans, at 1 and 5 days of adulthood. In C. elegans, only the TC-NER pathway is active in somatic cells since these animals do not carry out mitotic division after adulthood, and is therefore probably the most important in DNA repair. Knockdown of the csb-1, xpc-1 and xpa-1 genes was carried out using RNA interference (RNAi) using a system of modified bacteria containing plasmid DNA capable of synthesizing double-stranded RNA (dsRNA) in the LX929 strain (unc-17::GFP) which carries the green fluorescent protein (GFP) gene under the transcriptional control of the unc-17 promoter recognized only in cholinergic neurons. Neurodegeneration was analyzed by quantifying the fluorescence intensity and the integrity of the axonal projections of the neurons. No statistical difference was observed in the relative fluorescence intensity of the groups analyzed, but there was a high presence of bead-like structures along the cholinergic projections of the animals. In addition, animals treated with csb-1(RNAi) and xpc-1(RNAi) showed one only after 1 day of treatment. No neuronal loss was observed in the animals treated after 1 and 5 days of treatment, which may indicate that the neurodegenerative process does not result from neuronal loss in the first 5 days of treatment. Despite the absence of loss of neuronal mass, the accumulation of beads in the cholinergic projections opens the door to studies of new forms of neurodegeneration associated with inhibition of csb-1, xpa-1 and xpc-1.Attribution 3.0 Brazilhttp://creativecommons.org/licenses/by/3.0/br/NeurodegeneraçãoCSB-1XPC-1XPA-1RNAiNeurodegenerationCSB-1XPC-1XPA-1RNAibachelorThesisCNPQ::CIENCIAS BIOLOGICAS::GENETICA::MUTAGENESE