Creatine synthesis and exchanges between brain cells: What can be learned from human creatine deficiencies and various experimental models?

Details

Serval ID
serval:BIB_3467B6FD8F94
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Creatine synthesis and exchanges between brain cells: What can be learned from human creatine deficiencies and various experimental models?
Journal
Amino acids
Author(s)
Hanna-El-Daher L., Braissant O.
ISSN
1438-2199 (Electronic)
ISSN-L
0939-4451
Publication state
Published
Issued date
08/2016
Peer-reviewed
Oui
Volume
48
Number
8
Pages
1877-1895
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
While it has long been thought that most of cerebral creatine is of peripheral origin, the last 20 years has provided evidence that the creatine synthetic pathway (AGAT and GAMT enzymes) is expressed in the brain together with the creatine transporter (SLC6A8). It has also been shown that SLC6A8 is expressed by microcapillary endothelial cells at the blood-brain barrier, but is absent from surrounding astrocytes, raising the concept that the blood-brain barrier has a limited permeability for peripheral creatine. The first creatine deficiency syndrome in humans was also discovered 20 years ago (GAMT deficiency), followed later by AGAT and SLC6A8 deficiencies, all three diseases being characterized by creatine deficiency in the CNS and essentially affecting the brain. By reviewing the numerous and latest experimental studies addressing creatine transport and synthesis in the CNS, as well as the clinical and biochemical characteristics of creatine-deficient patients, our aim was to delineate a clearer view of the roles of the blood-brain and blood-cerebrospinal fluid barriers in the transport of creatine and guanidinoacetate between periphery and CNS, and on the intracerebral synthesis and transport of creatine. This review also addresses the question of guanidinoacetate toxicity for brain cells, as probably found under GAMT deficiency.

Keywords
Amidinotransferases/deficiency, Amidinotransferases/genetics, Amidinotransferases/metabolism, Amino Acid Metabolism, Inborn Errors/genetics, Amino Acid Metabolism, Inborn Errors/metabolism, Amino Acid Metabolism, Inborn Errors/pathology, Animals, Blood-Brain Barrier/metabolism, Blood-Brain Barrier/pathology, Brain Diseases, Metabolic, Inborn/genetics, Brain Diseases, Metabolic, Inborn/metabolism, Brain Diseases, Metabolic, Inborn/pathology, Capillaries/metabolism, Capillaries/pathology, Creatine/biosynthesis, Creatine/deficiency, Creatine/genetics, Creatine/metabolism, Developmental Disabilities/genetics, Developmental Disabilities/metabolism, Developmental Disabilities/pathology, Disease Models, Animal, Endothelial Cells/metabolism, Endothelial Cells/pathology, Guanidinoacetate N-Methyltransferase/deficiency, Guanidinoacetate N-Methyltransferase/genetics, Guanidinoacetate N-Methyltransferase/metabolism, Humans, Intellectual Disability/genetics, Intellectual Disability/metabolism, Intellectual Disability/pathology, Language Development Disorders/genetics, Language Development Disorders/metabolism, Language Development Disorders/pathology, Mental Retardation, X-Linked/genetics, Mental Retardation, X-Linked/metabolism, Mental Retardation, X-Linked/pathology, Movement Disorders/congenital, Movement Disorders/genetics, Movement Disorders/metabolism, Movement Disorders/pathology, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Plasma Membrane Neurotransmitter Transport Proteins/deficiency, Plasma Membrane Neurotransmitter Transport Proteins/genetics, Plasma Membrane Neurotransmitter Transport Proteins/metabolism, Speech Disorders/genetics, Speech Disorders/metabolism, Speech Disorders/pathology, AGAT, Blood brain barrier, Brain, Creatine, Creatine deficiency syndromes, GAMT, Guanidinoacetate, SLC6A8
Pubmed
Web of science
Create date
20/02/2016 15:31
Last modification date
20/08/2019 13:21
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