Astrocytes, SOD1 and Amyotrophic Lateral Sclerosis: Mechanisms and Implications in Neurodegeneration

Queiroz DD and Eleutherio ECA

Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Brazil

^*Correspondance to: Elis Cristina Araujo Eleutherio 

 PDF  Full Text Review Article | Open Access

Abstract:

As life expectancy increases, brain aging also rises, leading to cognitive and motor function decline. The accumulation of senescent glial cells during brain aging contributes to chronic inflammation and diseases such as Amyotrophic Lateral Sclerosis (ALS). These cells, including astrocytes, can undergo molecular and functional changes, exacerbating inflammation and inducing neuronal toxicity through the secretion of toxic factors, contributing to a pathogenic autotoxic cycle that drives disease progression. ALS, a severe neurodegenerative disease with reduced life expectancy, presents symptoms such as muscle atrophy, stiffness, and weakness due to motor neuron loss. ALS can be sporadic or familial, both linked directly or indirectly to Cu/Zn Superoxide Dismutase (SOD1) enzyme dysfunction. In addition to its role in eliminating superoxide radicals largely generated by respiration, SOD1 has been described as a possible transcription factor responsible for activating antioxidant protection mechanisms against oxidative stress. It is also implicated in signaling that shifts respiratory metabolism to aerobic glycolysis (glucose fermentation even in the presence of oxygen), affecting cellular protection against oxidative stress and longevity. Studies in animal models and post-mortem analyses of ALS patient tissues have demonstrated specific alterations in astrocytes, including changes in gene expression and secretion of pro-inflammatory factors. In summary, astrocytes play a complex and significant role in ALS, directly influencing disease progression through inflammatory processes, mitochondrial dysfunction, and oxidative stress. Better understanding of the roles of SOD1 and astrocytes in ALS pathogenesis is crucial for developing targeted therapeutic strategies aimed at modulating their protective and inflammatory functions.

Keywords:

Astrocyte; Superoxide dismutase 1; Amyotrophic Lateral Sclerosis and neurodegeneration

Cite the Article:

Queiroz DD and Eleutherio ECA. Astrocytes, SOD1 and Amyotrophic Lateral Sclerosis: Mechanisms and Implications in Neurodegeneration. Ann Clin Case Rep. 2024; 9: 2666..