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Redox Modifier Genes and Pathways in Amyotrophic Lateral Sclerosis
Journal article   Open access   Peer reviewed

Redox Modifier Genes and Pathways in Amyotrophic Lateral Sclerosis

Barrie J Carter, Pervin Anklesaria, Stephanie Choi and John F Engelhardt
Antioxidants & redox signaling, Vol.11(7), pp.1569-1586
07/2009
DOI: 10.1089/ars.2008.2414
PMCID: PMC2842588
PMID: 19187001
url
https://doi.org/10.1089/ars.2008.2414View
Published (Version of record) Open Access

Abstract

Enhanced redox-stress caused by neuroinflammation, mitochondria, and NADPH oxidases has been hypothesized to play critical roles in disease progression of amyotrophic lateral sclerosis (ALS). However, distinguishing whether the redox-stress observed in ALS is due to a primary defect in cellular reactive oxygen species metabolism/catabolism, or is a secondary consequence of neuroinflammation, has been difficult and the issue remains a matter of debate. Emerging evidence suggests that defects in genes that regulate NADPH oxidases may account for at least some forms of ALS. NADPH oxidases are key signaling complexes that influence cellular responses to growth factors and cytokines. In this context, NADPH oxidase-derived reactive oxygen species exert spatial control over the redox-dependent activation of certain pro-inflammatory receptors. Understanding the biology of how NADPH oxidases control cell signaling may help to clarify how genetic determinants of ALS lead to dysregulated pro-inflammatory signaling. This review provides a framework for understanding endosomal signaling through NADPH oxidases and potential mechanisms whereby gene defects in various forms of ALS may influence this cellular process and lead to motor neuron degeneration. Lastly, this review discusses past and current efforts to treat ALS using antioxidant therapies, as well as the limitations and advantages of each of these approaches. Antioxid. Redox Signal. 11, 1569–1586.
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