Modeling PKAN in Mice and Flies

Pantothenate kinase-associated neurodegeneration is an autosomal recessive disorder with progressive impairment of movement, vision, and cognition. The disease is the most common form of a clinically and genetically heterogeneous group of disorders named neurodegeneration with brain iron accumulation that share the distinctive feature of brain iron overload in the basal ganglia. Pantothenate kinase-associated neurodegeneration is caused by mutations in the pantothenate kinase 2 (PANK2), coding for the enzyme that phosphorylates vitamin B5 (pantothenate, pantothenic acid) in the first reaction of the coenzyme A biosynthetic pathway. In humans and mice, four genes express different isoforms of pantothenate kinase enzymes, which are targeted to different subcellular compartments. In Drosophila, a single pantothenate kinase gene encodes seven different isoforms responsible for all pantothenate kinase activity within the cell. Here, we describe what is known of the murine and Drosophila models, and we discuss their limits and possible exploitation as model systems to test experimental therapeutic approaches.