Sánchez, E., Azcona, L.J., Paisán-Ruiz, C. (2018) Pla2g6 Deficiency in Zebrafish Leads to Dopaminergic Cell Death, Axonal Degeneration, Increased β-Synuclein Expression, and Defects in Brain Functions and Pathways. Molecular neurobiology. 55(8):6734-6754.
This study aimed to gain insights into the pathophysiology underlying PLA2G6-associated neurodegeneration that is implicated in three different neurological disorders, suggesting that other, unknown genetic or environmental factors might contribute to its wide phenotypic expression. To accomplish this, we downregulated the function of pla2g6 in the zebrafish nervous system, performed parkinsonism-related phenotypic characterization, and determined the effects of gene regulation upon the loss of pla2g6 function by using RNA sequencing and downstream analyses. Pla2g6 deficiency resulted in axonal degeneration, dopaminergic and motor neuron cell loss, and increased β-synuclein expression. We also observed that many of the identified, differentially expressed genes were implicated in other brain disorders, which might explain the variable phenotypic expression of pla2g6-associated disease, and found that top enriched canonical pathways included those already known or suggested to play a major role in the pathogenesis of Parkinson's disease. Our data support that pla2g6 is relevant for cranial motor development with significant implications in the pathophysiology underlying Parkinson's disease.