Creatine deficiency syndromes and the importance of creatine synthesis in the brain.

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Serval ID
serval:BIB_CE3937F9A69E
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 deficiency syndromes and the importance of creatine synthesis in the brain.
Journal
Amino Acids
Author(s)
Braissant O., Henry H., Béard E., Uldry J.
ISSN
1438-2199 (Electronic)
ISSN-L
0939-4451
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
40
Number
5
Pages
1315-1324
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
Creatine deficiency syndromes, due to deficiencies in AGAT, GAMT (creatine synthesis pathway) or SLC6A8 (creatine transporter), lead to complete absence or very strong decrease of creatine in CNS as measured by magnetic resonance spectroscopy. Brain is the main organ affected in creatine-deficient patients, who show severe neurodevelopmental delay and present neurological symptoms in early infancy. AGAT- and GAMT-deficient patients can be treated by oral creatine supplementation which improves their neurological status, while this treatment is inefficient on SLC6A8-deficient patients. While it has long been thought that most, if not all, of brain creatine was of peripheral origin, the past years have brought evidence that creatine can cross blood-brain barrier, however, only with poor efficiency, and that CNS must ensure parts of its creatine needs by its own endogenous synthesis. Moreover, we showed very recently that in many brain structures, including cortex and basal ganglia, AGAT and GAMT, while found in every brain cell types, are not co-expressed but are rather expressed in a dissociated way. This suggests that to allow creatine synthesis in these structures, guanidinoacetate must be transported from AGAT- to GAMT-expressing cells, most probably through SLC6A8. This new understanding of creatine metabolism and transport in CNS will not only allow a better comprehension of brain consequences of creatine deficiency syndromes, but will also contribute to better decipher creatine roles in CNS, not only in energy as ATP regeneration and buffering, but also in its recently suggested functions as neurotransmitter or osmolyte.
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Web of science
Create date
09/03/2011 11:02
Last modification date
20/08/2019 16:48
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