Article: article from journal or magazin.
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: a review.
Journal of Inherited Metabolic Disease
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Creatine deficiency syndromes, either due to AGAT, GAMT or SLC6A8 deficiencies, lead to a complete absence, or a very strong decrease, of creatine within the brain, as measured by magnetic resonance spectroscopy. While the mammalian central nervous system (CNS) expresses AGAT, GAMT and SLC6A8, the lack of SLC6A8 in astrocytes around the blood-brain barrier limits the brain capacity to import creatine from the periphery, and suggests that the CNS has to rely mainly on endogenous creatine synthesis through AGAT and GAMT expression. This seems contradictory with SLC6A8 deficiency, which, despite AGAT and GAMT expression, also leads to creatine deficiency in the CNS. We present novel data showing that in cortical grey matter, AGAT and GAMT are expressed in a dissociated way: e.g. only a few cells co-express both genes. This suggests that to allow synthesis of creatine within the CNS, at least for a significant part of it, guanidinoacetate must be transported from AGAT- to GAMT-expressing cells, possibly through SLC6A8. This would explain the creatine deficiency observed in SLC6A8-deficient patients. By bringing together creatine deficiency syndromes, AGAT, GAMT and SLC6A8 distribution in CNS, as well as a synthetic view on creatine and guanidinoacetate levels in the brain, this review presents a comprehensive framework, including new hypotheses, on brain creatine metabolism and transport, both in normal conditions and in case of creatine deficiency.
Amidinotransferases/deficiency, Amidinotransferases/genetics, Amino Acid Metabolism, Inborn Errors/enzymology, Amino Acid Metabolism, Inborn Errors/genetics, Animals, Brain/enzymology, Creatine/deficiency, Developmental Disabilities/enzymology, Developmental Disabilities/genetics, Genetic Predisposition to Disease, Glycine/analogs & derivatives, Glycine/metabolism, Guanidinoacetate N-Methyltransferase/deficiency, Guanidinoacetate N-Methyltransferase/genetics, Humans, Intellectual Disability/enzymology, Intellectual Disability/genetics, Language Development Disorders/enzymology, Language Development Disorders/genetics, Membrane Transport Proteins/deficiency, Membrane Transport Proteins/genetics, Movement Disorders/congenital, Movement Disorders/enzymology, Phenotype, Prognosis, Speech Disorders/enzymology, Speech Disorders/genetics
Web of science
Last modification date