RNA-seq transcriptome of ZIKV-infected brain organoids reanalysis implicates Ndel1 oligopeptidase and its cytoskeleton protein binding partners in the infection pathogenesis and recovery following interferon treatment

Autor(es)

Nani, Joao, V ; Krenn, Veronica ; Christoff, Raissa R. ; Rabello, Tailene ; Garcez, Patricia P. ; Hayashi, Mirian A. F.

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1850, p. 6-pg., 2024-12-13.

Resumo

Neurogenesis defects contribute to neurodevelopmental disorders like autism, schizophrenia, and microcephaly. Microcephaly, marked by impaired brain development and fewer neuronal cells, predominantly affects the cerebral cortex, with around half of cases resulting from infections during early pregnancy. The protein Ndel1 (NudE Neurodevelopment Protein 1 Like 1), critical for neuronal migration, shows reduced activity in autism and schizophrenia and is similarly diminished in congenital Zika virus (ZIKV) syndrome models with microcephaly. Notably, Type I interferon treatment in these models restores Ndel1 activity, reversing microcephaly features. This suggests that Ndel1, its paralog Nde1, and related cytoskeleton proteins are involved in microcephaly, though their roles remain partially understood. To further investigate, we reanalyzed RNA-sequencing data from human brain organoids modeling ZIKV-induced microcephaly and interferon treatment. Differentially expressed genes (DEGs) analysis at various post-infection stages revealed significant expression changes in Nde1/Ndel1 pathway members after Zika infection, with restoration following interferon treatment. Our findings indicate that disruptions in Nde1/Ndel1-associated pathways, as shown in GO term analysis, contribute to virus- associated microcephaly and neurodevelopmental disorders, highlighting possible therapeutic interventions targeting altered Nde1/Ndel1 functions in related conditions. (AU)

• Processo FAPESP: 20/01107-7 - Estudo para otimização do uso da crotamina como teranóstico na terapia de doenças humanas: câncer, síndrome metabólica e disfunções renais
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/13112-8 - Estudo dos mecanismos moleculares e celulares em transtornos mentais: estudos clínicos e modelos animais
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 22/03297-3 - Explorando os mecanismos celulares e moleculares envolvidos nos transtornos do neurodesenvolvimento: investigando o papel do elemento de distribuição nuclear símile-1 (Ndel1)
• Beneficiário: João Victor Silva Nani
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 19/09207-3 - Estudo do(s) mecanismo(s) molecular(es) e celular(es) em transtornos mentais
• Beneficiário: João Victor Silva Nani
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 22/00527-8 - Atividade enzimática das oligopeptidases Ndel1 e/ou ECA no soro ou plasma de indivíduos com Depressão
• Beneficiário: Larissa Ribino Parra
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica