Inborn errors of coenzyme A metabolism and neurodegeneration
Ivano Di Meo
Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, Milan 20126, Italy
Search for more papers by this authorMiryam Carecchio
Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, Milan 20126, Italy
Department of Child Neurology, Foundation IRCCS Neurological Institute C. Besta, Via Celoria 11, Milan 20133, Italy
Department of Medicine and Surgery, PhD Programme in Molecular and Translational Medicine, University of Milan Bicocca, Via Cadore 48, Monza 20900, Italy
Search for more papers by this authorCorresponding Author
Valeria Tiranti
Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, Milan 20126, Italy
Correspondence
Valeria Tiranti, Unit of Molecular Neurogenetics, Foundation Neurological Institute C. Besta, Via Temolo 4, 20126 Milan, Italy.
Email: [email protected]
Search for more papers by this authorIvano Di Meo
Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, Milan 20126, Italy
Search for more papers by this authorMiryam Carecchio
Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, Milan 20126, Italy
Department of Child Neurology, Foundation IRCCS Neurological Institute C. Besta, Via Celoria 11, Milan 20133, Italy
Department of Medicine and Surgery, PhD Programme in Molecular and Translational Medicine, University of Milan Bicocca, Via Cadore 48, Monza 20900, Italy
Search for more papers by this authorCorresponding Author
Valeria Tiranti
Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, Milan 20126, Italy
Correspondence
Valeria Tiranti, Unit of Molecular Neurogenetics, Foundation Neurological Institute C. Besta, Via Temolo 4, 20126 Milan, Italy.
Email: [email protected]
Search for more papers by this authorFunding information Mariani Foundation; Telethon GGP16234
Abstract
Two inborn errors of coenzyme A (CoA) metabolism are responsible for distinct forms of neurodegeneration with brain iron accumulation (NBIA), a heterogeneous group of neurodegenerative diseases having as a common denominator iron accumulation mainly in the inner portion of globus pallidus. Pantothenate kinase-associated neurodegeneration (PKAN), an autosomal recessive disorder with progressive impairment of movement, vision and cognition, is the most common form of NBIA and is caused by mutations in the pantothenate kinase 2 gene (PANK2), coding for a mitochondrial enzyme, which phosphorylates vitamin B5 in the first reaction of the CoA biosynthetic pathway. Another very rare but similar disorder, denominated CoPAN, is caused by mutations in coenzyme A synthase gene (COASY) coding for a bi-functional mitochondrial enzyme, which catalyzes the final steps of CoA biosynthesis. It still remains a mystery why dysfunctions in CoA synthesis lead to neurodegeneration and iron accumulation in specific brain regions, but it is now evident that CoA metabolism plays a crucial role in the normal functioning and metabolism of the nervous system.
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