Recent progress in prion and prion-like protein aggregation

Abstract

Prion diseases and prion-like protein misfolding diseases involve the accumulation of abnormally aggregated forms of the normal host proteins, such as prion protein and Tau protein. These proteins are special because of their self-duplicating and transmissible characteristics. Such abnormally aggregated proteins mainly formed in neurons, cause the neurons dysfunction, and finally lead to invariably fatal neurodegenerative diseases. Prion diseases appear not only in animals, such as bovine spongiform encephalopathy in cattle and scrapie in sheep, but also in humans, such as Creutzfeldt -Jacob disease, and even the same prion or prion-like proteins can have many different phenotypes. A lot of biological evidence has suggested that the molecular basis for different strains of prions could be hidden in protein conformations, and the misfolded proteins with conformations different from the normal proteins have been proved to be the main cause for protein aggregation. Crowded physiological environments can be imitated in vitro to study how the misfolding of these proteins leads to the diseases in vivo. In this review, we provide an overview of the existing structural information for prion and prion-like proteins, and discuss the post-translational modifications of prion proteins and the difference between prion and other infectious pathogens. We also discuss what makes a misfolded protein become an infectious agent, and show some examples of prion-like protein aggregation, such as Tau protein aggregation and superoxide dismutase 1 aggregation, as well as some cases of prion-like protein aggregation in crowded physiological environments.

Response to stress in biological disorders: Implications of stress granule assembly and function

“… 74 In addition, proteins involved in RNA metabolism embody glutamine/asparagine (QN)‐rich domains, which can facilitate SGs assembly through self‐aggregation ability. 75 , 76 RNA‐binding proteins T‐cell intracellular antigen‐1 (TIA‐1), T‐cell intracellular antigen‐protein and their homologous proteins with conserved QN‐rich domains have been found in SGs, 77 , 78 among which TIA‐1 lacked the QN‐rich domain cannot support the formation of SGs. 75 , 76 In contrast, overexpression of the QN‐rich domain of TIA‐1 inhibits the regular assembly of SG and produces basic micro‐aggregates containing endogenous TIA proteins.…”

Sleep deprivation regulates availability of PrPC and Aβ peptides which can impair interaction between PrPC and laminin and neuronal plasticity

“…One of the common features observed in neurodegenerative diseases is aggregation and deposition of specific proteins such as infectious prion protein in transmissible spongiform encephalopathies (Yi, Xu, Chen, & Liang, ), Tau in Alzheimer´s disease (Iqbal et al, ) and α‐synuclein in Parkinson´s disease (Spillantini & Goedert, ). Normal functions of these proteins are often related to cell survival, differentiation, and neuronal activities (Bendor, Logan, & Edwards, ) (Guo, Noble, & Hanger, ) (Wulf, Senatore, & Aguzzi, ).…”