The identification of the genetic bases of PKAN and COPAN, two rare neurological disorders, is clear evidence that coenzyme A (CoA) biosynthesis and metabolism play a role in neural maintenance and functioning. PKAN is a disorder included in the NBIA (Neurodegeneration with Brain Iron Accumulation) category. PANK2, the mutated enzyme, catalyzes the first step in CoA biosynthesis. The identification of another mutated enzyme of this pathway, COASY, in NBIA patients confirms the relevance of CoA biosynthesis in these neurodegenerative processes. We recently analyzed the expression and function of pank2 in zebrafish; the gene is mainly present in the CNS and vascular system, and its down-regulation perturbs telencephalon, diencephalon and vessels formation. We also extended our analysis to coasy, the other involved gene. coasy shows ubiquitous embryonic expression, albeit with higher levels in CNS, somit es and notochord. coasy morphants display severe alterations in somites, notochord, CNS and anteroposterior axis. Interestingly, the addiction of CoA rescued a large percentage of morphants, confirming that a shortage of this metabolic precursor is the cause of the observed phenotype.
The role of CoA synthase during zebrafish development: possible insights into COPAN disorder
TISO, NATASCIA;ARGENTON, FRANCESCO;
2016
Abstract
The identification of the genetic bases of PKAN and COPAN, two rare neurological disorders, is clear evidence that coenzyme A (CoA) biosynthesis and metabolism play a role in neural maintenance and functioning. PKAN is a disorder included in the NBIA (Neurodegeneration with Brain Iron Accumulation) category. PANK2, the mutated enzyme, catalyzes the first step in CoA biosynthesis. The identification of another mutated enzyme of this pathway, COASY, in NBIA patients confirms the relevance of CoA biosynthesis in these neurodegenerative processes. We recently analyzed the expression and function of pank2 in zebrafish; the gene is mainly present in the CNS and vascular system, and its down-regulation perturbs telencephalon, diencephalon and vessels formation. We also extended our analysis to coasy, the other involved gene. coasy shows ubiquitous embryonic expression, albeit with higher levels in CNS, somit es and notochord. coasy morphants display severe alterations in somites, notochord, CNS and anteroposterior axis. Interestingly, the addiction of CoA rescued a large percentage of morphants, confirming that a shortage of this metabolic precursor is the cause of the observed phenotype.Pubblicazioni consigliate
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