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Review
. 2018 Jun 20:12:417.
doi: 10.3389/fnins.2018.00417. eCollection 2018.

Suppressor of Cytokine Signaling 3: Emerging Role Linking Central Insulin Resistance and Alzheimer's Disease

Lan Cao  1 , Zigao Wang  2 , Wenbin Wan  3
Affiliations
Review

Suppressor of Cytokine Signaling 3: Emerging Role Linking Central Insulin Resistance and Alzheimer's Disease

Lan Cao et al. Front Neurosci. .

Abstract

Currently, the etiology of Alzheimer's disease (AD) is still elusive. Central insulin resistance has been determined to play an important role in the progress of AD. However, the mechanism underlying the development of disrupted insulin signaling pathways in AD is unclear. Suppressor of cytokine signaling 3 (SOCS3) is a member of the SOCS protein family that acts as a negative modulator of insulin signaling in sensitive tissues, such as hepatocytes and adipocytes. However, little is known about its role in neurological diseases. Recent evidence indicates that the level of SOCS3 is increased in the brains of individuals with AD, especially in areas with amyloid beta deposition, suggesting that SOCS3 may regulate the central insulin signaling pathways in AD. Here, we discuss the potential role of SOCS3 in AD and speculate that SOCS3 may be a promising therapeutic target for the treatment of AD.

Keywords: Alzheimer’s disease; SOCS3; insulin resistance; neuroinflammation; therapeutic target.

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Figures

FIGURE 1
FIGURE 1
SOCS3 regulates insulin signaling in neuron. After receiving the stimulation of cytokines, the expression of SOCS3 is increased and then insulin signaling is disturbed by inhibiting the tyrosine phosphorylation process of IRS1. Furthermore, serine phosphorylation IRS1 is increased, which then results in the inflammatory effects and neuronal lesions.
FIGURE 2
FIGURE 2
The pattern of SOCS3 in the development of Alzheimer’s disease.
See this image and copyright information in PMC

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References

    1. Ali O., Cerjak D., Kent J. W., Jr., James R. (2016). Methylation of SOCS3 is inversely associated with metabolic syndrome in an epigenome-wide association study of obesity. Epigenetics 11 699–707. 10.1080/15592294.2016.1216284 - DOI - PMC - PubMed
    1. Babon J. J., Mcmanus E. J., Yao S., Desouza D. P. (2006). The structure of SOCS3 reveals the basis of the extended sh2 domain function and identifies an unstructured insertion that regulates stability. Mol. Cell 22 205–216. 10.1016/j.molcel.2006.03.024 - DOI - PubMed
    1. Bomfim T. R., Forny-Germano L., Sathler L. B., Brito-Moreira J. (2012). An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease- associated Abeta oligomers. J. Clin. Invest. 122 1339–1353. 10.1172/JCI57256 - DOI - PMC - PubMed
    1. Boucher J., Kleinridders A., Kahn C. R. (2014). Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb. Perspect. Biol 6:a009191. 10.1101/cshperspect.a009191 - DOI - PMC - PubMed
    1. Boyraz M., Yesilkaya E., Ezgu F., Bideci A. (2016). Effect of cytokine signaling 3 gene polymorphisms in childhood obesity. J. Clin. Res. Pediatr. Endocrinol. 8 452–460. 10.4274/jcrpe.3167 - DOI - PMC - PubMed

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