Infectivity versus Seeding in Neurodegenerative Diseases Sharing a Prion-Like Mechanism

Abstract

Prions are considered the best example to prove that the biological information can be transferred protein to protein through a conformational change. The term “prion-like” is used to describe molecular mechanisms that share similarities with the mammalian prion protein self-perpetuating aggregation and spreading characteristics. Since prions are presumably composed only of protein and are infectious, the more similar the mechanisms that occur in the different neurodegenerative diseases, the more these processes will resemble an infection. In vitro and in vivo experiments carried out during the last decade in different neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's diseases (PD), and amyotrophic lateral sclerosis (ALS) have shown a convergence toward a unique mechanism of misfolded protein propagation. In spite of the term “infection” that could be used to explain the mechanism governing the diversity of the pathological processes, other concepts as “seeding” or “de novo induction” are being used to describe the in vivo propagation and transmissibility of misfolded proteins. The current studies are demanding an extended definition of “disease-causing agents” to include those already accepted as well as other misfolded proteins. In this new scenario, “seeding” would be a type of mechanism by which an infectious agent can be transmitted but should not be used to define a whole “infection” process.

Amyloidogenic peptide homologous to fragment 129–148 of human myocilin

“…32 However, it is unlikely that such diseases are medically infectious in the same manner as prion diseases because (1) intracerebral inoculation experiments in primates did not transmit any neurodegenerative disease other than prion disease, 33 (2) epidemics of iatrogenic prion disease have not been accompanied by increases in the incidence of other neurodegenerative diseases (despite the higher overall prevalence of these diseases). 34 It is an intriguing possibility that the unique infectivity of mammalian prions may result from their interactions with specific cofactor molecules.…”

The Quest for Cellular Prion Protein Functions in the Aged and Neurodegenerating Brain

“…Kuru, Creutzfeldt-Jackob disease (CJD), Gertsmann-Straussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI) are diseases that occur in humans, while bovine spongiform encephalopathy (BSE) is found in cows, scrapie in sheep, and chronic wasting disease (CWD) in some members of the family Cervidae [7][8][9]. After the structural transition of PrP C , PrP Sc acquires self-aggregative, spreading (intercellular propagation), and infective (understood as a synonym of contagious) properties [10,11].…”

Morphological Changes of Glia in Prion and a Prion-Like Disorder

“…Current evidence supports the idea that many neurodegenerative diseases share specific features with prion diseases. Molecular mechanisms consisting of aggregation and spreading of misfolded proteins that are characteristic for each of them show similarities and, as a result, they have been included in a prion-like disease group [1]. Stanley Prusiner, the first scientist to identify the unique characteristics of prion disease, has even applied the term 'prion' to the specific aberrant proteins in each of these diseases that are the pathological hallmark, including β-amyloid in Alzheimer's and α-synuclein in Parkinson's disease [2,3].…”