Calcineurin Activation by Prion Protein Induces Neurotoxicity via Mitochondrial Reactive Oxygen Species.

Abstract

Prion diseases are caused by PrPsc accumulation in the brain, which triggers dysfunctional mitochondrial injury and reactive oxygen species (ROS) generation in neurons. Recent studies on prion diseases suggest that endoplasmic reticulum (ER) stress induced by misfolding proteins such as misfolded prion protein results in activation of calcineurin. Calcineurin is a calcium-related protein phosphatase of type 2B that exists in copious quantities in the brain and acts as a critical nodal component in the control of cellular functions. To investigate the relationship between calcineurin and intracellular ROS, we assessed the alteration of CaN and ROS induced by prion peptide (PrP) 106-126. Human prion peptide increased mitochondrial ROS by activating calcineurin, and the inhibition of calcineurin activity protected mitochondrial function and neuronal apoptosis in neuronal cells. These results suggest that calcineurin plays a pivotal role in neuronal apoptosis by mediating mitochondrial injury and ROS in prion diseases.

• Authors: Ji-Hong Moon, Jeong-Min Hong, Sang-Youel Park
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 5572129 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 34394828 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Ji-Hong Moon et al.

Chemical References

• Peptides
• Prion Proteins
• Reactive Oxygen Species
• Calcineurin
• Tacrolimus
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Apoptosis (drug effects)
• Calcineurin (metabolism)
• Cell Line, Tumor
• Cytosol (drug effects, metabolism)
• Humans
• Mitochondria (drug effects, metabolism)
• Peptides (chemical synthesis, pharmacology)
• Prion Proteins (chemistry)
• Reactive Oxygen Species (metabolism)
• Tacrolimus (pharmacology)
• Up-Regulation (drug effects)