FIGURE 1.

Neurodegenerative disorders associated to heme metabolism dysfunction. Schematic representation of the main pathways involved in the regulation of intracellular labile heme: heme synthesis, heme incorporation into hemoproteins, heme degradation, heme export and import. The picture highlights rare neurodegenerative disorders directly associated to heme metabolism dysfunction: defective heme biosynthesis causes neuropathic porphyria and is observed in FRDA; defective heme export (FLVCR1 mutations) is responsible for PCARP, RP and HSAN. For simplicity, these disorders have been depicted near FLVCR1a; however, the specific contribution of FLVCR1a and FLVCR1b to these disorders still remains to be addressed. Finally, defective heme import (FLVCR2 mutations) leads to the Fowler syndrome. Alteration of heme incorporation into hemoproteins and heme degradation have not been directly associated to a specific neurodegenerative disorder. However, we cannot exclude a role for these pathways in neurodegeneration.