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S-Nitrosylation in Alzheimer's disease

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Abstract

S-Nitrosylation, a redox-mediated posttranslational modification, is a result of the covalent binding nitric oxide (NO)-related species to cysteine residues of target proteins with the formation of nitrosothiols (SNOs). Normally, protein S-nitrosylation could be a cellular signaling mechanism, as is often a reversible and selective process, akin to protein phosphorylation. Emerging evidences have certified that the occurrence of aberrant S-nitrosylation of protein reactions could lead to protein misfolding, mitochondrial fission, synaptic damage, or apoptosis, thus contributing to the pathogenesis of Alzheimer’s disease (AD). In this review, we summarize the recent findings of key S-nitrosylated proteins which play crucial roles in the pathogenesis of AD and discuss how SNO proteins affect the progression of AD. In addition, it has been demonstrated that interference of S-nitrosylation could potentially protect from mitochondrial dysfunction, synaptic loss, or neuronal cell death in AD animal models. Hence, we also present the recent advances and challenges in targeting S-nitrosylated proteins for AD therapies.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81000544, 81171209, 81371406) and Shandong Provincial Natural Science Foundation, China (ZR2010HQ004, ZR2011HZ001).

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The authors declare no conflicts of interest.

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  1. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Qing-Fei Zhao, Jin-Tai Yu & Lan Tan

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Correspondence to Jin-Tai Yu or Lan Tan.

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Zhao, QF., Yu, JT. & Tan, L. S-Nitrosylation in Alzheimer's disease. Mol Neurobiol 51, 268–280 (2015). https://doi.org/10.1007/s12035-014-8672-2

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