Abstract
Amyloids are filamentous protein aggregates that are associated with a number of incurable diseases, termed amyloidoses. Amyloids can also manifest as infectious or heritable particles, known as prions. While just one prion is known in humans and animals, more than ten prion amyloids have been discovered in fungi. The propagation of fungal prion amyloids requires the chaperone Hsp104, though in excess it can eliminate some prions. Even though Hsp104 acts to disassemble prion fibrils, at normal levels it fragments them into multiple smaller pieces, which ensures prion propagation and accelerates prion conversion. Animals lack Hsp104, but disaggregation is performed by the same complement of chaperones that assist Hsp104 in yeast—Hsp40, Hsp70, and Hsp110. Exogenous Hsp104 can efficiently cooperate with these chaperones in animals and promotes disaggregation, especially of large amyloid aggregates, which indicates its potential as a treatment for amyloid diseases. However, despite the significant effects, Hsp104 and its potentiated variants may be insufficient to fully dissolve amyloid. In this review, we consider chaperone mechanisms acting to disassemble heritable protein aggregates in yeast and animals, and their potential use in the therapy of human amyloid diseases.
Highlights
Amyloids are filamentous protein aggregates with regular cross-beta type structure.They are generated from the soluble form of a single protein through self-catalytic structural conversion
Many amyloids are able to spread within an organism, or in certain tissues, showing prion-like properties [3,4], and there is emerging evidence that some can be infectious via direct injection [5]
The strain variations in such structures may be due to two partly dependent parameters: (a) the difference in the exact regions involved in the beta structure and (b) the different folding within a layer. The former parameter can be defined by several different methods, including fluorescent labels [49], hydrogen/deuterium exchange (HD) [50], and the resistance to proteinase K (PK) [45,50]
Summary
Amyloids are filamentous protein aggregates with regular cross-beta type structure. They are generated from the soluble form of a single protein through self-catalytic structural conversion. [PSI+ ], was discovered by Brian Cox in 1965 as an unusual nonsense-suppressor phenotype with non-Mendelian genetic properties [9] This phenotype segregated 4:0 in crosses of [PSI+ ] with non-prion [psi− ] cells; it could be spontaneously lost or cured with certain chemicals, as well as appearing de novo [10]. Another genetic element with similar behavior, [URE3], which allows the utilization of poor nitrogen sources in the presence of rich ones, was discovered by Francois Lacroute in 1971 [11]. We review existing data on how chaperones work to disassemble amyloids in yeast and animals, resulting in either amyloid dissolution or prion-like propagation, and the potential of chaperone-based mechanisms in therapies for human amyloid diseases and PD in particular
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
