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Multiomics approaches in Alexander disease zebrafish model show correlation between GFAP aggregation, altered lipid metabolism and oxidative stress

ABSTRACT: In this work we used our zebrafish model of Alexander Desease (AxD), aiming at unraveling the main pathways involved in AxD pathogenesis performing the first multi-omics analysis on a in vivo model of AxD. The obtained results have been functionally validated and they open the way to further investigation about the involvement of metabolic processes in AxD.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Danio Rerio (zebrafish) (brachydanio Rerio)

TISSUE(S): Embryo, Early Embryonic Cell

DISEASE(S): Alexander Disease

SUBMITTER: Gabriela Coronel Vargas

LAB HEAD: Tiziana Bachetti

PROVIDER: PXD040214 | Pride | 2025-03-03

REPOSITORIES: Pride

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A multi-omics approach reveals impaired lipid metabolism and oxidative stress in a zebrafish model of Alexander disease.

Bellitto Deianira D Bozzo Matteo M Ravera Silvia S Bertola Nadia N Rosamilia Francesca F Milia Jessica J Barboro Paola P Vargas Gabriela Coronel GC Di Lisa Donatella D Pastorino Laura L Lantieri Francesca F Castagnola Patrizio P Iervasi Erika E Ponassi Marco M Profumo Aldo A Tkachenko Kateryna K Rosano Camillo C Candiani Simona S Bachetti Tiziana T

Redox biology 20250213

Alexander disease (AxD) is a rare leukodystrophy caused by heterozygous mutations in the GFAP gene. To date, several in vitro and in vivo models have been generated in an attempt to unravel the main mechanisms underlying this complex disease. However, none of these models is suitable for investigating the global dysregulation caused by AxD. To address this shortcoming, we have generated a stable transgenic zebrafish line (zAxD) carrying the human GFAP p.R239C mutation, which is associated with s ...[more]

PMID: 40023981

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Gene expression changes associated with Alexander disease (AxD)

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Aberrant neurodevelopment in human iPS cell-derived models of Alexander disease

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