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Neuroprotective effect of Apelin 13 on ischemic stroke by activating AMPK/GSK-3β/Nrf2 signaling

Jialin Duan1,2, Jia Cui1, Zhifu Yang1

  • 1Department of Pharmacy, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, China.

Journal of Neuroinflammation
|February 3, 2019
PubMed
Abstract

Insights

Apelin 13 protects the brain from ischemic/reperfusion injury by activating the AMPK/GSK-3β/Nrf2 pathway, reducing inflammation and oxidative stress. This peptide therapy offers a promising neuroprotective strategy against stroke-related damage.

Area of Science:

  • Neuroscience
  • Cardiovascular Biology
  • Molecular Biology

Background:

  • Ischemic/reperfusion (I/R) injury is a major cause of stroke.
  • Apelin 13 has shown potential in protecting against apoptosis in I/R models.
  • The precise mechanisms of Apelin 13's neuroprotection in brain I/R were not fully understood.

Purpose of the Study:

  • To investigate if Apelin 13 protects against brain I/R injury.
  • To elucidate the role of the AMPK/GSK-3β/Nrf2 pathway in Apelin 13's protective effects.
  • To identify upstream signaling molecules involved in Apelin 13's mechanism.

Main Methods:

  • Established an in vivo rat model of I/R and administered Apelin 13 intracerebroventricularly.
  • Assessed neurobehavioral scores, infarct volumes, brain edema, and cytokine levels.
  • Utilized PC12 cells for in vitro studies, employing proteases inhibitors and siRNA to investigate the AMPK/GSK-3β/Nrf2 pathway and upstream signaling.

Main Results:

  • Apelin 13 significantly reduced infarct size, brain edema, apoptosis, oxidative stress, and neuroinflammation post-I/R.
  • Apelin 13 increased Nrf2 expression and phosphorylation of AMPK and GSK-3β.
  • Silencing Nrf2 or inhibiting AMPK abolished Apelin 13's protective effects, confirming the pathway's importance.

Conclusions:

  • Apelin 13 confers neuroprotection against I/R injury by activating the AMPK/GSK-3β pathway.
  • This activation upregulates Nrf2-regulated antioxidant enzymes, mitigating ROS-mediated inflammation and oxidative stress.
  • The upstream signaling cascade involves AR/Gα/PLC/IP3/CaMKK, highlighting a novel therapeutic target.
Keywords:
AMPK/GSK-3β/Nrf2Apelin 13InflammationIschemic strokeOxidative stress

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