The role of glutathione redox imbalance in autism spectrum
disorder: A review

J 2020

The role of glutathione redox imbalance in autism spectrum disorder: A review

BJORKLUND, G., A. A. TINKOV, B. HOSNEDLOVA, René KIZEK, O. P. AJSUVAKOVA et. al.

Basic information

Original name

The role of glutathione redox imbalance in autism spectrum disorder: A review

Authors

BJORKLUND, G. (guarantor), A. A. TINKOV, B. HOSNEDLOVA, René KIZEK (203 Czech Republic, belonging to the institution), O. P. AJSUVAKOVA, S. CHIRUMBOLO, M. G. SKALNAYA, M. PEANA, M. DADAR, A. EL-ANSARY, H. QASEM, J. B. ADAMS, J. AASETH and A. V. SKALNY

Edition

Free Radical Biology and Medicine, NEW YORK, ELSEVIER SCIENCE INC, 2020, 0891-5849

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.376

RIV identification code

RIV/00216224:14160/20:00118454

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.1016/j.freeradbiomed.2020.07.017

UT WoS

000595854700015

Keywords in English

Autism; GSH:GSSG ratio; Antioxidant capacity; Oxidative stress

Abstract

V originále

The role of glutathione in autism spectrum disorder (ASD) is emerging as a major topic, due to its role in the maintenance of the intracellular redox balance. Several studies have implicated glutathione redox imbalance as a leading factor in ASD, and both ASD and many other neurodevelopmental disorders involve low levels of reduced glutathione (GSH), high levels of oxidized glutathione (GSSG), and abnormalities in the expressions of glutathione-related enzymes in the blood or brain. Glutathione metabolism, through its impact on redox environment or redox-independent mechanisms, interferes with multiple mechanisms involved in ASD pathogenesis. Glutathione-mediated regulation of glutamate receptors [e.g., N-methyl-D-aspartate (NMDA) receptor], as well as the role of glutamate as a substrate for glutathione synthesis, may be involved in the regulation of glutamate excitotoxicity. However, the interaction between glutathione and glutamate in the pathogenesis of brain diseases may vary from synergism to antagonism. Modulation of glutathione is also associated with regulation of redox-sensitive transcription factors nuclear factor kappa B (NF-kappa B) and activator protein 1 (AP-1) and downstream signaling (proinflammatory cytokines and inducible enzymes), thus providing a significant impact on neuroinflammation. Mitochondrial dysfunction, as well as neuronal apoptosis, may also provide a significant link between glutathione metabolism and ASD. Furthermore, it has been recently highlighted that glutathione can affect and modulate DNA methylation and epigenetics. Review analysis including research studies meeting the required criteria for analysis showed statistically significant differences between the plasma GSH and GSSG levels as well as GSH:GSSG ratio in autistic patients compared with healthy individuals (P = 0.0145, P = 0.0150 and P = 0.0202, respectively). Therefore, the existing data provide a strong background on the role of the glutathione system in ASD pathogenesis. Future research is necessary to investigate the role of glutathione redox signaling in ASD, which could potentially also lead to promising therapeutics.

Citovat

BJORKLUND, G., A. A. TINKOV, B. HOSNEDLOVA, René KIZEK, O. P. AJSUVAKOVA, S. CHIRUMBOLO, M. G. SKALNAYA, M. PEANA, M. DADAR, A. EL-ANSARY, H. QASEM, J. B. ADAMS, J. AASETH and A. V. SKALNY. The role of glutathione redox imbalance in autism spectrum disorder: A review. Free Radical Biology and Medicine. NEW YORK: ELSEVIER SCIENCE INC, 2020, vol. 160, No 1, p. 149-162. ISSN 0891-5849. Available from: https://dx.doi.org/10.1016/j.freeradbiomed.2020.07.017.

@article{1755484,
   author = {Bjorklund, G. and Tinkov, A. A. and Hosnedlova, B. and Kizek, René and Ajsuvakova, O. P. and Chirumbolo, S. and Skalnaya, M. G. and Peana, M. and Dadar, M. and ElandAnsary, A. and Qasem, H. and Adams, J. B. and Aaseth, J. and Skalny, A. V.},
   article_location = {NEW YORK},
   article_number = {1},
   doi = {http://dx.doi.org/10.1016/j.freeradbiomed.2020.07.017},
   keywords = {Autism; GSH:GSSG ratio; Antioxidant capacity; Oxidative stress},
   language = {eng},
   issn = {0891-5849},
   journal = {Free Radical Biology and Medicine},
   title = {The role of glutathione redox imbalance in autism spectrum disorder: A review},
   url = {https://pubmed.ncbi.nlm.nih.gov/32745763/#:~:text=Several%20studies%20have%20implicated%20glutathione,related%20enzymes%20in%20the%20blood},
   volume = {160},
   year = {2020}
}

TY  - JOUR
ID  - 1755484
AU  - Bjorklund, G. - Tinkov, A. A. - Hosnedlova, B. - Kizek, René - Ajsuvakova, O. P. - Chirumbolo, S. - Skalnaya, M. G. - Peana, M. - Dadar, M. - El-Ansary, A. - Qasem, H. - Adams, J. B. - Aaseth, J. - Skalny, A. V.
PY  - 2020
TI  - The role of glutathione redox imbalance in autism spectrum disorder: A review
JF  - Free Radical Biology and Medicine
VL  - 160
IS  - 1
SP  - 149-162
EP  - 149-162
PB  - ELSEVIER SCIENCE INC
SN  - 08915849
KW  - Autism
KW  - GSH:GSSG ratio
KW  - Antioxidant capacity
KW  - Oxidative stress
UR  - https://pubmed.ncbi.nlm.nih.gov/32745763/#:~:text=Several%20studies%20have%20implicated%20glutathione,related%20enzymes%20in%20the%20blood
N2  - The role of glutathione in autism spectrum disorder (ASD) is emerging as a major topic, due to its role in the maintenance of the intracellular redox balance. Several studies have implicated glutathione redox imbalance as a leading factor in ASD, and both ASD and many other neurodevelopmental disorders involve low levels of reduced glutathione (GSH), high levels of oxidized glutathione (GSSG), and abnormalities in the expressions of glutathione-related enzymes in the blood or brain. Glutathione metabolism, through its impact on redox environment or redox-independent mechanisms, interferes with multiple mechanisms involved in ASD pathogenesis. Glutathione-mediated regulation of glutamate receptors [e.g., N-methyl-D-aspartate (NMDA) receptor], as well as the role of glutamate as a substrate for glutathione synthesis, may be involved in the regulation of glutamate excitotoxicity. However, the interaction between glutathione and glutamate in the pathogenesis of brain diseases may vary from synergism to antagonism. Modulation of glutathione is also associated with regulation of redox-sensitive transcription factors nuclear factor kappa B (NF-kappa B) and activator protein 1 (AP-1) and downstream signaling (proinflammatory cytokines and inducible enzymes), thus providing a significant impact on neuroinflammation. Mitochondrial dysfunction, as well as neuronal apoptosis, may also provide a significant link between glutathione metabolism and ASD. Furthermore, it has been recently highlighted that glutathione can affect and modulate DNA methylation and epigenetics. Review analysis including research studies meeting the required criteria for analysis showed statistically significant differences between the plasma GSH and GSSG levels as well as GSH:GSSG ratio in autistic patients compared with healthy individuals (P = 0.0145, P = 0.0150 and P = 0.0202, respectively). Therefore, the existing data provide a strong background on the role of the glutathione system in ASD pathogenesis. Future research is necessary to investigate the role of glutathione redox signaling in ASD, which could potentially also lead to promising therapeutics.
ER  -

BJORKLUND, G., A. A. TINKOV, B. HOSNEDLOVA, René KIZEK, O. P. AJSUVAKOVA, S. CHIRUMBOLO, M. G. SKALNAYA, M. PEANA, M. DADAR, A. EL-ANSARY, H. QASEM, J. B. ADAMS, J. AASETH and A. V. SKALNY. The role of glutathione redox imbalance in autism spectrum disorder: A review. \textit{Free Radical Biology and Medicine}. NEW YORK: ELSEVIER SCIENCE INC, 2020, vol.~160, No~1, p.~149-162. ISSN~0891-5849. Available from: https://dx.doi.org/10.1016/j.freeradbiomed.2020.07.017.

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