Nat Commun: A beta protein structure reveals its toxicity

, July 2, 2020 /PRNewswire/ --- -- The brains of millions of people with Alzheimer's disease (AD) are slowly and inevitably running out of neurons, leading to a characteristic loss of memory and cognitive function associated with the condition, however, the cause of neuronal death is still unknownAvailable treatments are designed to slow the development of dementia and can only help improve short-term quality of lifeTherefore, the actual treatment of acure AD is an unmet medical need(photo: www.
.com)in a recent study, Natalia Carulla et alrevealed for the first time the structure of amyloid beta (A-beta) assembly proteinsUnderstanding of this structure reveals new toxic mechanisms for these assemblies, namely the ability to disrupt neuronal membranes, allow water and ions to penetrate and cause cell deathsome studies suggest that the interaction of Beta proteins with neuronal membranes is the cause of neuronal death observed in ADIn order to solve the instability of different conformations, the team first studied A-beta protein in a simplified model system that simulates neuronal membranes, and prepared a stable form of A-beta with uniform composition and shapeOnce the different components were identified, they studied the structure and patterns of their neurotoxicity and established a 3D arrangement of all atoms that make up the A-beta collection"Our study shows that certain A-beta associations can penetrate the neuronal membranes and alter their osmosis balance, triggering death," said Sonia Ciudad and Eduard Puig, the paper's lead authorsCiudad is currently a research and development scientist at Werfen BiokitPuig is now a postdoctoral fellow at the IRB Asymmetrical Synthesis Research Group in Barcelonathe study focused on two Beta proteins, one consisting of four A-beta protein sub-subtones and the other consisting of eight, whose arrangement has the ability to destroy cell membranes, making them key to causing Neurodegeneration of ADFurther work should focus on ways to prevent the formation of such ensembles, thereby preventing membrane rupture(Bio Valley Bioon.com)Source:3D Structure of A beta protein protein perise sa new mechanism of toxicity
original source:Ciudad, S., et al(2020)A beta (1-42) tetramer and octamer structuresiumNature Communications.
doi.org/10.1038/s41467-020-16566-1.