Banca de QUALIFICAÇÃO: CESAR ORLANDO MUÑOZ CADAVID

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : CESAR ORLANDO MUÑOZ CADAVID
DATA : 22/08/2019
HORA: 14:00
LOCAL: ANFITEATRO DOS PEIXES
TÍTULO:

A DEFINIR

PALAVRAS-CHAVES:

Alzheimer's disease, Huntington's disease, BER and NER pathways and Caenorhabditis elegans.

PÁGINAS: 113
GRANDE ÁREA: Ciências Biológicas
ÁREA: Genética
RESUMO:

The integrity of our genetic material is under constant attack from numerous endogenous and exogenous agents. The consequences of a defective DNA damage response are well studied in proliferating cells, especially with regards to the development of cancer, yet its precise roles in the nervous system are relatively poorly understood. The objective of this work was to evaluate the role of BER and NER pathways in the development of neurodegenerative phenotypes in the transgenic of C. elegans models for Alzheimer's disease and Huntington's disease. The role of BER and NER pathways was assessed by knockdown of the apn-1 and exo-3 (BER pathway), xpc-1, csb-1 and xpa-1 (of the NER pathway) genes. The knockdown of the BER and NER repair genes through RNAi accentuates the phenotypes of neurodegenerative diseases in the nematode C. elegans, showing a greater effect when the inhibition is done on the genes of the NER system. Simultaneous inhibition of repair genes by double RNAi further accentuate phenotypes compared to the use of single RNAi. This effect was greatest when using double RNAi for the XPA/ BER systems and the NER system combinations. Also, the absence of these genes affected the redox status of the animals by increasing ROS levels, mitochondrial membrane potential and GST-4 expression. Increased ROS and GST-4 levels were dependent on the presence of SKN-1, one transcription factor in response to stress. Proteolytic activity of RNAi-treated animals was decreased with respect to control, especially in animals with absence of xpa-1 and xpa-1;exo-3 genes (**** p <0.0001). Finally, stress response target gene levels such as gst-4, sod-3 and papr-1 were increased in RNAi-treated animals for the xpa-1 and xpa-1;exo-3 genes, interestingly, an opposite effect was obtained when expression levels of genes involved in proteolytic and lysosomal degradation such as ubh-1, vha-8, pas-4 and pbs-4 were evaluated. These data suggest that BER and NER repair pathways play an important role in the development of neurodegenerative phenotypes in transgenic C. elegans models for MA and DH. This effect may be due to the redox state imbalance and the transcriptional regulation of some genes in response to oxidative stress and genes involved in proteolytic and lysosomal activity.

MEMBROS DA BANCA:
Presidente - 1997012 - RAQUEL CORDEIRO THEODORO
Interna - 1674709 - VIVIANE SOUZA DO AMARAL
Externa ao Programa - 1837354 - JULLIANE TAMARA ARAUJO DE MELO CAMPOS