PMCA Applications for Prion Detection in Peripheral Tissues of Patients with Variant Creutzfeldt-Jakob Disease

Abstract

Prion diseases are neurodegenerative and invariably fatal conditions that affect humans and animals. In particular, Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE) are paradigmatic forms of human and animal prion diseases, respectively. Human exposure to BSE through contaminated food caused the appearance of the new variant form of CJD (vCJD). These diseases are caused by an abnormal prion protein named PrPSc (or prion), which accumulates in the brain and leads to the onset of the disease. Their definite diagnosis can be formulated only at post-mortem after biochemical and neuropathological identification of PrPSc. Thanks to the advent of an innovative technique named protein misfolding cyclic amplification (PMCA), traces of PrPSc, undetectable with the standard diagnostic techniques, were found in peripheral tissues of patients with vCJD, even at preclinical stages. The technology is currently being used in specialized laboratories and can be exploited for helping physicians in formulating an early and definite diagnosis of vCJD using peripheral tissues. However, this assay is currently unable to detect prions associated with the sporadic CJD (sCJD) forms, which are more frequent than vCJD. This review will focus on the most recent advances and applications of PMCA in the field of vCJD and other human prion disease diagnosis.

Inactivation of Scrapie Prions by the Electrically Charged Disinfectant CAC-717

“…Here we examined the ability of CAC-717 to inactivate prion proteins. Western blotting was used for PrP Sc analysis, and protein misfolding cyclic amplification (PMCA), which mimics the in vivo reaction and amplifies PrP Sc in vitro [28][29][30], was used to examine the seeding activity of PrP Sc . In both assays, PK-resistant PrP (PrPres) was used as an indicator of PrP Sc .…”

The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells

“…Some studies have investigated prion pathogenesis and neurotoxic pathways in vivo using Rocky Mountain Laboratory (RML) infection and antibody-derived anti-PrP ligands ( 61 – 63 ). In these studies, the neurodegenerative changes typical of prion diseases were observed without detectable PrPsc, suggesting the presence of additional mechanisms of neuronal death in prion disorders, aside from those related to PrPsc ( 64 , 65 ). We suggest that prion peptide may have valuable role as a therapeutic strategy for prion diseases though PrP (106–126) is not equivalent to PrPsc.…”

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

“…Previous literature has investigated prion pathogenesis and neurotoxic pathways using Rocky Mountain Laboratory (RML) strain and antibody-derived anti-PrP ligands in in vivo models [51][52][53]. Typical neurodegenerative fluctuations in prion diseases have been observed in the absence of detectable PrPsc, suggesting that prion disorders are caused by alternative mechanisms of neuronal damage, as well as PrPsc [54,55]. PrP 106-126 has been suggested as one such alternative contributor to the pathogenic and molecular properties of PrPsc [56].…”