Nigral transcriptomic profiles in Engrailed-1 hemizygous mouse models of Parkinson's disease reveal upregulation of oxidative phosphorylation-related genes associated with delayed dopaminergic neurodegeneration.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, increasing both in terms of prevalence and incidence. To date, only symptomatic treatment is available, highlighting the need to increase knowledge on disease etiology in order to develop new therapeutic strategies. Hemizygosity for the gene Engrailed-1 ( Transcriptome profiles were defined by RNAseq in microdissected substantia nigra from 1-week old OF1, OF1- Nigrostriatal neurodegeneration was manifested in OF1- Our results suggest that increased expression of genes encoding mitochondrial proteins before the onset of neurodegeneration is associated with increased resistance to PD-like nigrostriatal neurodegeneration. This highlights the importance of genetic background in PD models, how different strains can be used to model clinical and sub-clinical pathologies and provides insights to gene expression mechanisms associated with PD susceptibility and progression.

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Copyright © 2024 Belfiori, Dueñas Rey, Ralbovszki, Jimenez-Ferrer, Fredlund, Balikai, Ahrén, Brolin and Swanberg.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.