Prions: Beyond a Single Protein

Abstract

SUMMARYSince the term protein was first coined in 1838 and protein was discovered to be the essential component of fibrin and albumin, all cellular proteins were presumed to play beneficial roles in plants and mammals. However, in 1967, Griffith proposed that proteins could be infectious pathogens and postulated their involvement in scrapie, a universally fatal transmissible spongiform encephalopathy in goats and sheep. Nevertheless, this novel hypothesis had not been evidenced until 1982, when Prusiner and coworkers purified infectious particles from scrapie-infected hamster brains and demonstrated that they consisted of a specific protein that he called a “prion.” Unprecedentedly, the infectious prion pathogen is actually derived from its endogenous cellular form in the central nervous system. Unlike other infectious agents, such as bacteria, viruses, and fungi, prions do not contain genetic materials such as DNA or RNA. The unique traits and genetic information of prions are believed to be encoded within the conformational structure and posttranslational modifications of the proteins. Remarkably, prion-like behavior has been recently observed in other cellular proteins—not only in pathogenic roles but also serving physiological functions. The significance of these fascinating developments in prion biology is far beyond the scope of a single cellular protein and its related disease.

Axonal changes in experimental prion diseases recapitulate those following constriction of postganglionic branches of the superior cervical ganglion: a comparison 40 years later

“…As in many neurodegenerative diseases caused by the accumulation of 'toxic' misfolded proteins [8,9] prion diseases die via programmed cell death of which only the apoptotic process is relatively well understood. According to the recommendations of the Nomenclature Committee on Cell Death [10][11][12], three major types of programmed cell death (PCD) can be discriminated.…”

Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease

“…Human prion diseases include Creutzfeldt-Jakob disease (CJD), fatal insomnia, Gerstmann-Sträussler-Scheinker syndrome, kuru, and variably protease-sensitive prionopathy (2). The etiology can be sporadic, acquired by infection, or inherited.…”

Characterization of physiochemical properties of caveolin-1 from normal and prion-infected human brains

“…Compared to untreated sample, the protein migrated faster at ˜21 kDa in the sample treated with 5 μg/ml while the protein in the samples treated with PK from 25 - 2,000 μg/ml migrated consistently at 20 kDa (Figure 3A ). The change in molecular weight of caveolin-1 caused by PK-treatment suggests that part of the caveolin-1 molecule is removed by the PK-digestion due to PK-sensitivity while other part is resistant to PK-digestion, a phenomenon called partial PK-resistance characteristic of the PrP Sc molecule [ 6 ]. There was no difference in the PK-resistance of caveolin-1 between non-CJD and CJD brain samples (Figure 3A ).…”