1. The structural line between prion and "prion-like": Insights from prion protein and tau.
- Author
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Glynn, Calina, Rodriguez, Jose A., and Hyman, Bradley T.
- Subjects
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TAU proteins , *PRIONS , *PRION diseases , *TAUOPATHIES , *AMYLOID - Abstract
The concept of 'prion-like' behavior has emerged in the study of diseases involving protein misfolding where fibrillar structures, called amyloids, self-propagate and induce disease in a fashion similar to prions. From a biological standpoint, in order to be considered 'prion-like,' a protein must traverse cells and tissues and further propagate via a templated conformational change. Since 2017, cryo-electron microscopy structures from patient-derived 'prion-like' amyloids, in particular tau, have been presented and revealed structural similarities shared across amyloids. Since 2021, cryo-EM structures from prions of known infectivity have been added to the ex vivo amyloid structure family. In this review, we discuss current proposals for the 'prion-like' mechanisms of spread for tau and prion protein as well as discuss different influencers on structures of aggregates from tauopathies and prion diseases. Lastly, we discuss some of the current hypotheses for what may distinguish structures that are 'prion-like' from transmissible prion structures. • Prion-like aggregates exit, are taken up, and propagate across cells and tissues. • Tau fibril structures point to isoform-composition-based structural patterns. • Prion strains share structural similarities despite host prion sequence variation. • GSS harbors a distinct structure to those of scrapie-derived prion strains. • A structural line between prion and prion-like may be thin. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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