Page 68 - Q. Neuroscience

[Q. Neuroscience-40]

Calcineurin activation by prion protein induces NF-κB-driven

proinflammatory response through autophagy pathway

Jeong-Min Hong¹, Ji-Hong Moon¹, Sang-Youel Park¹

¹Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Republic

of Korea

Prion diseases are fatal neurodegenerative disorders that are caused by accumulation of abnormal prion protein
(PrPSc) in the brain. Recent studies have illustrated that calcineurin could play an important role in the calcium-

calmodulin pathway to regulate nuclear factor kappa B (NF-κB). Calcineurin is activated by the binding of calcium

to calmodulin. In the present study, we examined the activation of calcineurin and autophagy upon exposure to
prion peptide, and their roles in prion peptide-induced upregulation of nuclear factor-kappa B (NF-κB) and
proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, in human neurocarcinoma.

The results indicate that prion peptide induces calcineurin activation, which subsequently leads to the activation of
NF-κB transcription factor. Calcineurin activation increased the expression of TNF-α and IL-6, which was blocked by

treatment with calcineurin inhibitor and autophagy inhibitor. Collectively, our results show that calcineurin activation
mediated by prion protein induces NF-κB-driven neuroinflammation via autophagy pathway, suggesting that

calcineurin and autophagy may be possible therapeutic targets for neuroinflammation in neurodegeneration
diseases including prion disease.