Cristian A Lasagna-Reeves, Maxime WC Rousseaux ... Huda Y Zoghbi
Studies in a mouse model of spinocerebellar ataxia type 1 show that a protein called capicua stabilizes toxic ataxin-1 oligomers offering a possible explanation for regional patterns of neurodegeneration.
Andisheh Abedini, Annette Plesner ... Ann Marie Schmidt
Toxic IAPP intermediates have some molecular features that are similar to, and others that are distinct from, toxic species reported for other amyloidogenic polypeptides.
By using structural methods to screen compounds for their ability to interact with amyloid beta, researchers have identified small molecules that stabilize amyloid fibers and reduce the toxic effect of smaller aggregates on cells.
Monitoring the formation of two distinct arrangements in early amyloid-ß aggregation by mass spectrometry and ion mobility allows determination of the effect of potential drug candidates.
The polyQ tract of pathogenic Huntingtin causes aggregation when expanded in Huntington’s disease, but its two flanking domains control its conformational landscape, proteostasis and neurotoxicity.
Cristian A Lasagna-Reeves, Maxime WC Rousseaux ... Huda Y Zoghbi
Building on previous work (Lasagna-Reeves et al., 2015) it is shown that polyglutamine ATXN1 oligomers propagate locally in SCA1 mice, and that passive immunotherapy targeting soluble oligomers can lead to an improvement in motor coordination and a modest increase in life span.
Pascal Krotee, Jose A Rodriguez ... David S Eisenberg
Atomic structures of hIAPP fibrillar segments, determined using the cryo electron microscopy method MicroED, reveal that strong, stable intermolecular interactions are important features of cytotoxic amyloid proteins.
Amyloid beta, the major component of plaques in Alzheimer's disease, acutely and reversibly signals to modulate sleep as a function of oligomeric length, independently of neuronal loss.