» Articles » PMID: 34201812

Glutathione in the Nervous System As a Potential Therapeutic Target to Control the Development and Progression of Amyotrophic Lateral Sclerosis

Overview
Date 2021 Jul 2
PMID 34201812
Citations 23
Authors
Affiliations
Soon will be listed here.
Abstract

Amyotrophic lateral sclerosis (ALS) is a rare neurological disorder that affects the motor neurons responsible for regulating muscle movement. However, the molecular pathogenic mechanisms of ALS remain poorly understood. A deficiency in the antioxidant tripeptide glutathione (GSH) in the nervous system appears to be involved in several neurodegenerative diseases characterized by the loss of neuronal cells. Impaired antioxidant defense systems, and the accumulation of oxidative damage due to increased dysfunction in GSH homeostasis are known to be involved in the development and progression of ALS. Aberrant GSH metabolism and redox status following oxidative damage are also associated with various cellular organelles, including the mitochondria and nucleus, and are crucial factors in neuronal toxicity induced by ALS. In this review, we provide an overview of the implications of imbalanced GSH homeostasis and its molecular characteristics in various experimental models of ALS.

Citing Articles

TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro.

Duan Q, Wang H, Su W, Gu X, Shen X, Jiang Z BMC Med. 2024; 22(1):96.

PMID: 38443977 PMC: 10916235. DOI: 10.1186/s12916-024-03314-1.


Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.

Xiang Y, Song X, Long D Arch Toxicol. 2024; 98(3):579-615.

PMID: 38265475 PMC: 10861688. DOI: 10.1007/s00204-023-03660-8.


Dietary Marine Oils Selectively Decrease Obesogenic Diet-Derived Carbonylation in Proteins Involved in ATP Homeostasis and Glutamate Metabolism in the Rat Cerebellum.

Moreno F, Mendez L, Raner A, Miralles-Perez B, Romeu M, Ramos-Romero S Antioxidants (Basel). 2024; 13(1).

PMID: 38247527 PMC: 10812471. DOI: 10.3390/antiox13010103.


An Update on Glutathione's Biosynthesis, Metabolism, Functions, and Medicinal Purposes.

Gasmi A, Nasreen A, Lenchyk L, Lysiuk R, Peana M, Shapovalova N Curr Med Chem. 2023; 31(29):4579-4601.

PMID: 37921175 DOI: 10.2174/0109298673251025230919105818.


Effects of Acetyl-L-Carnitine on Oxidative Stress in Amyotrophic Lateral Sclerosis Patients: Evaluation on Plasma Markers and Members of the Neurovascular Unit.

Grossini E, De Marchi F, Venkatesan S, Mele A, Ferrante D, Mazzini L Antioxidants (Basel). 2023; 12(10).

PMID: 37891966 PMC: 10604350. DOI: 10.3390/antiox12101887.


References
1.
Srinivasan S, Shariff M, Bartlett S . The role of the glucocorticoids in developing resilience to stress and addiction. Front Psychiatry. 2013; 4:68. PMC: 3730062. DOI: 10.3389/fpsyt.2013.00068. View

2.
Miller V, Lawrence D, Mondal T, Seegal R . Reduced glutathione is highly expressed in white matter and neurons in the unperturbed mouse brain--implications for oxidative stress associated with neurodegeneration. Brain Res. 2009; 1276:22-30. PMC: 2744579. DOI: 10.1016/j.brainres.2009.04.029. View

3.
Sautin Y, Johnson R . Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucleic Acids. 2008; 27(6):608-19. PMC: 2895915. DOI: 10.1080/15257770802138558. View

4.
Bannai S . Exchange of cystine and glutamate across plasma membrane of human fibroblasts. J Biol Chem. 1986; 261(5):2256-63. View

5.
Kraft A, Johnson D, Johnson J . Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J Neurosci. 2004; 24(5):1101-12. PMC: 6793572. DOI: 10.1523/JNEUROSCI.3817-03.2004. View