Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities.

Antioxid Redox Signal

1 The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Published: April 2019

AI Article Synopsis

  • Reactive oxygen, nitrogen, and sulfur species are gaining recognition for their vital roles in cellular functions, particularly in neurodegeneration, where redox imbalance can lead to harmful signaling and stress responses.
  • Recent advances have highlighted redox-regulated processes and post-translational modifications that enhance our understanding of neuroprotection, opening up potential therapeutic avenues for neurodegenerative diseases.
  • Despite this progress, a precise understanding of redox-related events and the development of methodologies for accurate detection of reactive species in vivo remain critical challenges.

Article Abstract

Significance: Once considered to be mere by-products of metabolism, reactive oxygen, nitrogen and sulfur species are now recognized to play important roles in diverse cellular processes such as response to pathogens and regulation of cellular differentiation. It is becoming increasingly evident that redox imbalance can impact several signaling pathways. For instance, disturbances of redox regulation in the brain mediate neurodegeneration and alter normal cytoprotective responses to stress. Very often small disturbances in redox signaling processes, which are reversible, precede damage in neurodegeneration. Recent Advances: The identification of redox-regulated processes, such as regulation of biochemical pathways involved in the maintenance of redox homeostasis in the brain has provided deeper insights into mechanisms of neuroprotection and neurodegeneration. Recent studies have also identified several post-translational modifications involving reactive cysteine residues, such as nitrosylation and sulfhydration, which fine-tune redox regulation. Thus, the study of mechanisms via which cell death occurs in several neurodegenerative disorders, reveal several similarities and dissimilarities. Here, we review redox regulated events that are disrupted in neurodegenerative disorders and whose modulation affords therapeutic opportunities.

Critical Issues: Although accumulating evidence suggests that redox imbalance plays a significant role in progression of several neurodegenerative diseases, precise understanding of redox regulated events is lacking. Probes and methodologies that can precisely detect and quantify in vivo levels of reactive oxygen, nitrogen and sulfur species are not available.

Future Directions: Due to the importance of redox control in physiologic processes, organisms have evolved multiple pathways to counteract redox imbalance and maintain homeostasis. Cells and tissues address stress by harnessing an array of both endogenous and exogenous redox active substances. Targeting these pathways can help mitigate symptoms associated with neurodegeneration and may provide avenues for novel therapeutics. Antioxid. Redox Signal. 30, 1450-1499.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393771PMC
http://dx.doi.org/10.1089/ars.2017.7321DOI Listing

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