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Author Spotlight: Insight Into Advances in Prion Diseases Research
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Author Spotlight: Insight Into Advances in Prion Diseases Research

Published on: August 11, 2023

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Melatonin protects mesenchymal stem cells from autophagy-mediated death under ischaemic ER-stress conditions by

Jun Hee Lee1, Yeo Min Yoon2, Yong-Seok Han2

  • 1Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.

Cell Proliferation
|November 16, 2018
PubMed
Abstract

Insights

Melatonin protects mesenchymal stem cells (MSCs) from ischemic injury by reducing endoplasmic reticulum (ER) stress and autophagy. This protection, mediated by cellular prion protein (PrPC), enhances tissue repair and limb recovery.

Area of Science:

  • Cellular and Molecular Biology
  • Regenerative Medicine
  • Biochemistry

Background:

  • Ischaemic injuries trigger endoplasmic reticulum (ER) stress and autophagy in mesenchymal stem cells (MSCs).
  • MSC dysfunction under ER stress and autophagy limits their therapeutic potential for ischaemic diseases.

Purpose of the Study:

  • To investigate melatonin's protective effects on MSCs against ER stress and autophagy.
  • To evaluate the role of cellular prion protein (PrPC) in melatonin's protective mechanism.
  • To assess the therapeutic efficacy of melatonin-treated MSCs in a murine hindlimb ischaemia model.

Main Methods:

  • In vitro analysis of MSC viability, apoptosis, and autophagy markers under melatonin treatment.
  • Establishment of a murine hindlimb ischaemia model to evaluate in vivo effects.
  • Assessment of ER stress and autophagy-associated protein expression, including PrPC.

Main Results:

  • Melatonin suppressed ER stress and autophagy by upregulating PrPC expression, inhibiting apoptotic cell death in MSCs.
  • Melatonin enhanced MnSOD and catalase activity in MSCs.
  • Melatonin-treated MSCs improved functional limb recovery and neovascularization in vivo, effects blocked by PrPC knockdown.

Conclusions:

  • Melatonin protects MSCs from ER stress/autophagy-induced apoptosis via augmented PrPC expression.
  • Melatonin-treated MSCs represent a promising cell-based therapy for ER stress-related ischaemic diseases.
  • Melatonin-induced PrPC is a key mediator in ameliorating ER stress and autophagy.
Keywords:
autophagycellular prion proteinendoplasmic reticulum stressmelatoninmesenchymal stem cell

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