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Creutzfeldt-Jakob Disease (and Other Prion Diseases)
Published in Alexander R. Toftness, Incredible Consequences of Brain Injury, 2023
Variably protease-sensitive prionopathy (VPSPr) is another prion disease that was recently discovered (Gambetti et al., 2008). It wasn't until 2010 that it was conclusively shown to be a group of similar-but-slightly different versions of the same prion, each with differences in their sensitivity to being digested, leading to the word “variably” being used in their description (Zou et al., 2010). It has been suggested that VPSPr closely resembles GSS in some respects, and may be a sporadic variant of that generally familial prion disease (Nonno et al., 2019). In other words, anyone can get it if they are really unlucky.
3-Nitrotyrosine: a versatile oxidative stress biomarker for major neurodegenerative diseases
Published in International Journal of Neuroscience, 2020
Maria Bandookwala, Pinaki Sengupta
Human prion diseases or transmissible spongiform encephalopathies (TSEs) is a rare condition originating either spontaneously, due to genetically altered proteome, cellular stress response or by infection [69]. It is a group of fatal neurodegenerative diseases with approximately 1 death in a million people annually according to worldwide epidemiological data published by WHO. It includes transmissible and progressive degenerative disorders of the CNS like Kuru, fatal familial insomnia, variably protease-sensitive prionopathy (VPSPr), Gerstmann–Sträussler–Scheinker syndrome and sporadic and variant Creutzfeldt-Jakob disease among which sporadic CJD is the most common form [70]. Rapidly developing dementia, confusion, hallucinations, muscle stiffness, difficulty in speaking and shuffling gait are the symptoms affecting the quality of life of people. A clinical study by Chen et al. [71] in China revealed that patient usually dies on an average of 7.1 months after disease which coincided with the reports from epidemiological studies in the west. Damage to the nerve cells is central to the manifestation of prion disease typically characterized by the accumulation of mutated prion protein PrPSc. OS has long been recognized as a molecular and cellular mechanism as a driving force in the pathophysiology of prion disease. In vivo immunohistochemical studies by D. R. Brown in scrapie-infected mice model backed with supporting evidence validate the role of OS via confirmation of the presence of OS biomarkers [72]. Brown also conducted in vitro studies, and similar results were obtained from scrapie-infected cells where reduced levels of antioxidants were observed making the cells more vulnerable to the damage by free radicals [72]. Protein profiling experiments have revealed expressional alteration of DJ-1, an antioxidant protein and its nuclear translocalization due to OS in sCJD. Tahir et al. [73] observed a significantly higher amount of DJ-1 in the CSF of clinical sCJD patients. The same research group also detected DJ-1 upregulation in humanized PrP transgenic mice model at the pre-symptomatic and symptomatic stages indicative of OS [73]. Global metabolic profiling conducted in the hippocampus and cortex of prion protein-infected mice by Bourgognon et al. [74]showed alteration in glucose metabolism, upregulation of NO signalling, downregulation of SOD1 and SOD2 antioxidant genes which contribute to oxidative and nitrosative stress. Figure 5 shows the OS mechanism in TSE.