Redesigning therapies for pantothenate kinase–associated neurodegeneration |
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Authors: | Muhammad I Munshi Sarah J Yao Choukri Ben Mamoun |
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Institution: | Section of Infectious Diseases, Department of Internal Medicine and Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA |
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Abstract: | Pantothenate kinase–associated neurodegeneration (PKAN) is an incurable rare genetic disorder of children and young adults caused by mutations in the PANK2 gene, which encodes an enzyme critical for the biosynthesis of coenzyme A. Although PKAN affects only a small number of patients, it shares several hallmarks of more common neurodegenerative diseases of older adults such as Alzheimer''s disease and Parkinson''s disease. Advances in etiological understanding and treatment of PKAN could therefore have implications for our understanding of more common diseases and may shed new lights on the physiological importance of coenzyme A, a cofactor critical for the operation of various cellular metabolic processes. The large body of knowledge that accumulated over the years around PKAN pathology, including but not limited to studies of various PKAN models and therapies, has contributed not only to progress in our understanding of the disease but also, importantly, to the crystallization of key questions that guide future investigations of the disease. In this review, we will summarize this knowledge and demonstrate how it forms the backdrop to new avenues of research. |
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Keywords: | neurodegeneration pantothenate kinase– associated neurodegeneration coenzyme A iron mitochondria gene therapy drug design Alzheimer''s disease Parkinson''s disease |
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