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

• Published in: Oxidative medicine and cellular longevity Vol. 2021; no. 1; p. 5572129
• Main Authors: Moon, Ji-Hong, Hong, Jeong-Min, Park, Sang-Youel
• Format: Journal Article
• Language: English
• Published: United States Hindawi 2021; Hindawi Limited
• Subjects: Acetylcysteine - pharmacology; Alzheimer's disease; Antibodies; Apoptosis; Apoptosis - drug effects; Calcineurin - metabolism; Cell Line, Tumor; Cytosol - drug effects; Cytosol - metabolism; Endoplasmic reticulum; Flow cytometry; Humans; Medical research; Microscopy; Mitochondria - drug effects; Mitochondria - metabolism; Neurotoxicity; Oxidative stress; Peptides; Peptides - chemical synthesis; Peptides - pharmacology; Phosphatase; Prion Proteins - chemistry; Proteins; Reactive Oxygen Species - metabolism; Tacrolimus - pharmacology; Up-Regulation - drug effects; Variance analysis; Grand Island New York; St Louis Missouri; France; United States > US
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2021/5572129

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.