Creutzfeldt-Jakob Disease (and Other Prion Diseases)
Alexander R. Toftness in Incredible Consequences of Brain Injury, 2023
Prions cause damage as they tangle together and form plaques in the brain. Why do prions damage the brain, but the proteins that they are formed from don't? The protein that the prions discussed in this chapter form out of is a 253-amino-acid chain called PrP that serves a purpose in the cell membranes of human cells (Scheckel & Aguzzi, 2018). Usually, when those proteins are done serving their purpose, they dissolve. Prions are just PrP but twisted into a slightly different shape, often called “misfolded” because the chain of amino acids looks like it has a different fold in it (Ma & Wang, 2014). This changed shape makes them resistant to dissolving, a trait called “protease-resistant” (Scheckel & Aguzzi, 2018). Therefore, the reason that prions build up and form dangerous plaques in the brain is because they can't be dissolved and cleared away, eventually suffocating and killing brain cells (Rhodes, 1998, p. 197). That's why the spongiform holes appear in the brains of people with prion diseases, because the dead cells leave behind holes.
Prions
Dongyou Liu in Handbook of Foodborne Diseases, 2018
The most feasible method to prevent this disease from spreading, either via human-to-human or zoonotic transmission, is by active surveillance and improvement in the diagnostic methods in terms of sensitivity and specificity. There are many foods (especially beef and beef-related products), chemicals, blood products, and so on, related to TSE, and the amount of prion agents contained therein is small, so a further increase in sensitivity of the assays is required. Recent developments in diagnostic methods such as PMCA and RT-QuIC have the potential to facilitate sensitive detection of prions in these samples. In addition, further developments of inactivation methods for prion agents are also important in reducing the risks of secondary infection with prion agents. Alternatively, to prevent the production of prion-contaminated materials, there is a clear need to develop sensitive methods capable of identifying BSE at an early presymptomatic stage of the disease. Then, prion-contaminated materials should be subjected to incineration as soon as possible to eliminate the prions.
Formulating the prion hypothesis
Kiheung Kim in The Social Construction of Disease, 2006
Prusiner's decision to suggest a new name for the agent reflected a wider sense among scrapie researchers that they were working on something peculiar and important. This is, in turn, apparent in a general interest in inventing a new classification for the agent. Between the late 1970s and early 1980s, several attempts were made to give the agent a proper name. In 1979, the Edinburghbased researchers, including Alan Dickinson, Richard Kimberlin and George Outram, suggested calling it a ‘virino’, a name that suggests that it is related to viruses but that highlights its peculiarities, especially its small size (Dickinson and Outram 1979). Other scientists in the field called it a ‘slow (unconventional) virus’. Prusiner and his team took the opportunity of their 1982 Science article to suggest a different name for the infectious agent which made no reference to any supposed viral characteristics, but instead pointed to particular biochemical properties of the agent. Stanley Prusiner suggested calling it ‘prion’ (pronounced pree-on). According to him, prions are small proteinaceous infectious particles that are resistant to inactivation by most procedures that modify nucleic acids. The term ‘prion’ underscores the requirement of a protein for infection; current knowledge does not allow exclusion of a small nucleic acid within the interior of the particle.(Prusiner 1982a: 141)
Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Dong Hwan Kim, Jaehyeon Kim, Hakmin Lee, Dongyun Lee, So Myoung Im, Ye Eun Kim, Miryeong Yoo, Yong-Pil Cheon, Jason C. Bartz, Young-Jin Son, Eun-Kyoung Choi, Yong-Sun Kim, Jae-Ho Jeon, Hyo Shin Kim, Sungeun Lee, Chongsuk Ryou, Tae-gyu Nam
Prions are the infectious protein that cause prion diseases, including bovine spongiform encephalopathy, scrapie, and Creutzfeldt–Jakob disease (CJD)1,2. The clinical signs of prion diseases are related to impaired brain function, such as cognitive dysfunction, cerebral ataxia and motor dysfunction1,3. The neuropathological features of prion diseases include spongiform degeneration and gliosis in accociation with the accumulation of PrPsc in the brain4. Recent studies at the cellular and molecular levels report that spongiosis and neurodegeneration are caused by prion-induced chronic endoplasmic reticulum (ER) stress leading to the depletion of an intracellular lipid molecule and impaired lysosomal trafficking in brain cells5,6.
Recent advances in cellular models for discovering prion disease therapeutics
Published in Expert Opinion on Drug Discovery, 2022
Lea Nikolić, Chiara Ferracin, Giuseppe Legname
Following the discovery of PrP as the major prion disease-causing agent, other proteins, in diverse organisms, were identified as proteinaceous infectious particles (prions). Although these proteins have different primary sequences and functions, they share many similarities with the disease-causing prions. For instance, they are PK resistant, they can spread their misfolded conformation to the native isoform, they exist in multiple distinct variants, and they can spread from one cell to another and its progeny. In yeasts, at least ten prions have been identified so far. The most studied yeast prions are Saccharomyces Cerevisiae [URE3], the prion form of Ure2p (a protein involved in the regulation of nitrogen metabolism), and [PSI+], the prion form of Sup35 (a translation termination factor); but also other engineered yeast prions have been developed. An example is an engineered Sup35 protein fused to various regions of the mouse PrP protein [107,108].
Ultrasensitive techniques and protein misfolding amplification assays for biomarker-guided reconceptualization of Alzheimer’s and other neurodegenerative diseases
Published in Expert Review of Neurotherapeutics, 2021
Nicole Campese, Maria Francesca Beatino, Claudia Del Gamba, Elisabetta Belli, Linda Giampietri, Eleonora Del Prete, Alessandro Galgani, Andrea Vergallo, Gabriele Siciliano, Roberto Ceravolo, Harald Hampel, Filippo Baldacci
Prions are ‘small proteinaceous infectious particles, which are resistant to inactivation by most procedures that modify nucleic acids’ according to Stanley Prusiner’s definition [27]. First described in the late sixties by Alper and Griffith in their main biochemical and biological features and recognized as the pathogenic agents of scrapie [28–30], prions consist of PrPsc, pathological aggregates of the misfolded Cellular Prion Protein (PrPc) [31]. PrPc may undergo misfolding and aberrant aggregation processes, under still not completely clarified pathophysiological mechanisms, leading to the formation of β-sheet-rich oligomers. These may subsequently promote PrPc misfolding and aggregation into highly ordered protofibrils and fibrils [31]. Protofibrils and fibrils may decay into smaller fragments acting as nucleating agents, inducing further spreading of the aberrant proteins based on sequential nucleation–fragmentation cycles [31].
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