Abstract
Prion diseases and prion- like protein misfolding diseases are related to the accumulation of abnormal aggregates of the normal host proteins including prion proteins and Tau protein. These proteins possess self-templating and transmissible characteristics. The crowded physiological environments where the aggregation of these amyloidogenic proteins takes place can be imitated in vitro by the addition of macromolecular crowding agents such as inert polysaccharides. In this review, we summarize the aggregation of prion proteins in crowded physiological environments and discuss the role of macromolecular crowding in prion protein aggregation. We also summarize the aggregation of prion- like proteins including human Tau protein, human α-synuclein, and human copper, zinc superoxide dismutase under macromolecular crowding environments and discuss the role of macromolecular crowding in prion- like protein aggregation. The excluded-volume effects caused by macromolecular crowding could accelerate the aggregation of neurodegenerative disease-associated proteins while inhibiting the aggregation of the proteins that are not neurodegenerative disease-associated.
Highlights
Folded and functional proteins are the most important executors in a series of biological processes ranging from the synthesis of all kinds of biological molecules to cellular signalInt
We suggest that the strong inhibition of fibrillization of the rabbit prion protein (PrP) by the crowded physiological environment and the absence of such a protease-resistant fragment for the rabbit PrP could be two of the reasons why rabbits are resistant to prion diseases [15]
Prion diseases and prion- like protein misfolding diseases are resulted from the accumulation of abnormal aggregates of amyloidogenic proteins such as prion protein and Tau protein with self-templating and transmissible characteristics
Summary
During folding and processing in specific compartments after being synthesized in cells, incompletely folded proteins will inevitably be exposed to the solvent and interact with other molecules inappropriately and those off-pathway partially folded proteins could either be saved by cellular quality control mechanisms including molecular chaperones or degraded by cellular quality control mechanisms including proteasomes [4,5]. Should they escape such cellular quality control mechanisms, they will form aggregates with abnormal conformations [6]. As neurodegenerative diseases are related to the self-association and fibrillization of amyloidogenic proteins, it is necessary to imitate crowded physiological environments where aggregation of such proteins takes place by the addition of macromolecular crowding agents in vitro [11,12,13,14,15,16,17,18,19,20,21,22]
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