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

Author(s)

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

• Document type: Journal article
• Source: Brain Research; v. 1850, p. 6-pg., 2024-12-13.

Abstract

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)

• FAPESP's process: 20/01107-7 - Study to optimize the use of crotamine as a theranostic in the therapy of human diseases: cancer, metabolic syndrome and renal dysfunction
• Grantee: Mirian Akemi Furuie Hayashi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/13112-8 - Study of molecular and cellular mechanisms involved in mental disorders: clinical and animal models analysis
• Grantee: Mirian Akemi Furuie Hayashi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/03297-3 - Exploring the molecular and cellular mechanism(s) underlying neurodevelopmental disorders: investigating the role(s) of Nuclear Distribution Element like-1 (Ndel1)
• Grantee: João Victor Silva Nani
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 19/09207-3 - Study of molecular and cellular mechanisms in mental disorders
• Grantee: João Victor Silva Nani
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/00527-8 - Enzymatic activity of oligopeptidases Ndel1 and/or ACE in plasma or blood serum of patients with Depression
• Grantee: Larissa Ribino Parra
• Support Opportunities: Scholarships in Brazil - Scientific Initiation