4.3 Review

Possibility that the Onset of Autism Spectrum Disorder is Induced by Failure of the Glutamine-Glutamate Cycle

Journal

CURRENT MOLECULAR PHARMACOLOGY
Volume 14, Issue 2, Pages 170-174

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1874467213666200319125109

Keywords

Autism spectrum disorder; glutamine-glutamate cycle; endoplasmic reticulum stress

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Autism spectrum disorder (ASD) is a neurodevelopmental disease with increasing prevalence, likely caused by genetic and environmental factors. Endoplasmic reticulum stress and amino acid cycle abnormalities may play a role in the development of ASD. Theanine, a derivative of glutamine, may prevent the onset of ASD by altering the balance of glutamine and glutamate in the brain.
Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients has increased rapidly in recent years. The causes of ASD involve both genetic and environmental factors, but the details of causation have not yet been fully elucidated. Many reports have investigated genetic factors related to synapse formation, and alcohol and tobacco have been reported as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle abnormalities (particularly glutamine and glutamate) induced by many environmental factors. In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand, one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine-glutamate cycle is performed between neurons and glial cells and controls the concentration of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse formation and are important in constructing neural circuits. Theanine is a derivative of glutamine and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent the onset of ASD by changing the balance of glutamine and glutamate in the brain.

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