: Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disease. Cell damage in ALS is the result of many different, largely unknown, pathogenetic mechanisms. Astrocytes and microglial cells play a critical role also for their ability to enhance a deranged inflammatory response. Excitotoxicity, due to excessive glutamate levels and increased intracellular Ca2+ concentration, has also been proposed to play a key role in ALS pathogenesis/progression. Reactive Oxygen Species (ROS) behave as key second messengers for multiple receptor/ligand interactions. ROS-dependent regulatory networks are usually mediated by peroxides. Superoxide Dismutase 1 (SOD1) physiologically mediates intracellular peroxide generation. About 10% of ALS subjects show a familial disease associated with different gain-of-function SOD1 mutations. The occurrence of sporadic ALS, not clearly associated with SOD1 defects, has been also described. SOD1-dependent pathways have been involved in neuron functional network as well as in immune-response regulation. Both, neuron depolarization and antigen-dependent T-cell activation mediate SOD1 exocytosis, inducing increased interaction of the enzyme with a complex molecular network involved in the regulation of neuron functional activity and immune response. Here, alteration of SOD1-dependent pathways mediating increased intracellular Ca2+ levels, altered mitochondria functions and defective inflammatory process regulation have been proposed to be relevant for ALS pathogenesis/progression.

Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis / Rubino, V.; La Rosa, G.; Pipicelli, L.; Carriero, F.; Damiano, S.; Santillo, M.; Terrazzano, G.; Ruggiero, G.; Mondola, P.. - In: ANTIOXIDANTS. - ISSN 2076-3921. - 12:9(2023), p. 1747. [10.3390/antiox12091747]

Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis

Rubino V.;La Rosa G.;Damiano S.;Santillo M.;Terrazzano G.;Ruggiero G.;Mondola P.
2023

Abstract

: Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disease. Cell damage in ALS is the result of many different, largely unknown, pathogenetic mechanisms. Astrocytes and microglial cells play a critical role also for their ability to enhance a deranged inflammatory response. Excitotoxicity, due to excessive glutamate levels and increased intracellular Ca2+ concentration, has also been proposed to play a key role in ALS pathogenesis/progression. Reactive Oxygen Species (ROS) behave as key second messengers for multiple receptor/ligand interactions. ROS-dependent regulatory networks are usually mediated by peroxides. Superoxide Dismutase 1 (SOD1) physiologically mediates intracellular peroxide generation. About 10% of ALS subjects show a familial disease associated with different gain-of-function SOD1 mutations. The occurrence of sporadic ALS, not clearly associated with SOD1 defects, has been also described. SOD1-dependent pathways have been involved in neuron functional network as well as in immune-response regulation. Both, neuron depolarization and antigen-dependent T-cell activation mediate SOD1 exocytosis, inducing increased interaction of the enzyme with a complex molecular network involved in the regulation of neuron functional activity and immune response. Here, alteration of SOD1-dependent pathways mediating increased intracellular Ca2+ levels, altered mitochondria functions and defective inflammatory process regulation have been proposed to be relevant for ALS pathogenesis/progression.
2023
Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis / Rubino, V.; La Rosa, G.; Pipicelli, L.; Carriero, F.; Damiano, S.; Santillo, M.; Terrazzano, G.; Ruggiero, G.; Mondola, P.. - In: ANTIOXIDANTS. - ISSN 2076-3921. - 12:9(2023), p. 1747. [10.3390/antiox12091747]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/940747
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