Creatine, central nervous system and creatine deficiency syndromes

摘要

It was long thought that most of brain creatine was of peripheral origin. However, recent works have demonstrated that creatine crosses blood-brain barrier only with poor efficiency, and that CNS must ensure parts of its creatine needs by its own creatine synthesis pathway, thank to the brain expression of AGAT and GAMT (creatine synthesis) and SLC6A8 (creatine transporter). This new understanding of creatine metabolism and transport in CNS allows a better comprehension of creatine deficiency syndromes, which are due to deficiencies in AGAT, GAMT and SLC6A8 and mainly affect the brain of patients who show severe neurodevelopmental delay and present neurological symptoms in early infancy.