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Review
. 2024 Jan 29:15:1320086.
doi: 10.3389/fphys.2024.1320086. eCollection 2024.

Oxidative stress and ion channels in neurodegenerative diseases

Razan Orfali  1 , Adnan Z Alwatban  1 , Rawan S Orfali  2 , Liz Lau  3 , Noble Chea  3 , Abdullah M Alotaibi  1 , Young-Woo Nam  3 , Miao Zhang  3
Affiliations
Review

Oxidative stress and ion channels in neurodegenerative diseases

Razan Orfali et al. Front Physiol. .

Abstract

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson's, Alzheimer's, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington's disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly investigated for their functional responses to oxidizing agents and oxidative stress. This review primarily explores the relationship and potential links between oxidative stress and ion channels in neurodegenerative conditions, such as cerebellar ataxias and Parkinson's disease. The potential correlation between oxidative stress and ion channels could hold promise for developing innovative therapies for common neurodegenerative diseases.

Keywords: antioxidants; calcium channel; glutathione; neurodegenerative disorders; oxidative stress; potassium channels; reactive oxygen species; sodium channels.

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Conflict of interest statement

Author RSO is a member of BrainExperiments.com. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Oxidative stress and neurodegenerative diseases (Ashok et al., 2022). An imbalance between ROS/RNS and antioxidants damages lipids, proteins, and DNA. Cellular apoptosis and tissue death are promoted by impaired mitochondrial function and buildup of activated astrocytes and microglia. BBB, Blood Brain Barrier.
FIGURE 2
FIGURE 2
Topology diagrams of some ion channel families, showing locations of transmembrane domains and pore-forming segments. Transmembrane, (TM).
FIGURE 3
FIGURE 3
Pathophysiological consequences of redox modulation of some ion channels (Akbarali, 2014). Cysteine (CyS), Store-operated Ca2+ release-activated Ca2+ (CRAC) channels or (Orai 1 channels). Tetrodotoxin-resistant (TTX-R) Na+ (NaV1.9) TTX-R.
See this image and copyright information in PMC

References

    1. Aborode A. T., Pustake M., Awuah W. A., Alwerdani M., Shah P., Yarlagadda R., et al. (2022). Targeting oxidative stress mechanisms to treat alzheimer’s and Parkinson’s disease: a critical review. Oxid. Med. Cell Longev. 2022, 7934442. 10.1155/2022/7934442 - DOI - PMC - PubMed
    1. Adelman J. P., Clapham D. E., Hibino H., Inanobe A., Jan L. Y., Karschin A., et al. (2023). Inwardly rectifying potassium channels (KIR) in GtoPdb v.2023.1. IUPHARBPS Guide Pharmacol. CITE 2023. 10.2218/gtopdb/F74/2023.1 - DOI
    1. Adibhatla R. M., Hatcher J. F. (2010). Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal 12, 125–169. 10.1089/ars.2009.2668 - DOI - PubMed
    1. Aggarwal P., Singh S., Ravichandiran V. (2021). Two-pore domain potassium channel in neurological disorders. J. Membr. Biol. 254, 367–380. 10.1007/s00232-021-00189-8 - DOI - PubMed
    1. Akbarali H. (2014). Oxidative stress and ion channels. Syst. Biol. Free Radic. Antioxid., 355–373. 10.1007/978-3-642-30018-9_12 - DOI