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Free keywords:
CELLULAR PRION PROTEIN; MOLECULAR CHAPERONES; NMR STRUCTURE;
BETA-2-ALPHA-2 LOOP; EXPANSION PROTEINS; UBIQUITIN SYSTEM;
ALPHA-SYNUCLEIN; DISEASES; PROTEOSTASIS; AGGREGATIONchaperones; conformational disease; NMR spectroscopy; prion proteins;
protein aggregation; X-ray crystallography;
Abstract:
Amyloid diseases are characterized by the accumulation of insoluble, -strand-rich aggregates. The underlying structural conversions are closely associated with cellular toxicity, but can also drive the formation of functional protein assemblies. In recent years, studies in the field of structural studies have revealed astonishing insights into the origins, mechanisms and implications of amyloid formation. Notably, high-resolution crystal structures of peptides in amyloid-like fibrils and prefibrillar oligomers have become available despite their challenging chemical nature. Nuclear magnetic resonance spectroscopy has revealed that dynamic local polymorphisms in the benign form of the prion protein affect the transformation into amyloid fibrils and the transmissibility of prion diseases. Studies of the structures and interactions of chaperone proteins help us to understand how the cellular proteostasis network is able to recognize different stages of aberrant protein folding and prevent aggregation. In this review, we will focus on recent developments that connect the different aspects of amyloid biology and discuss how understanding the process of amyloid formation and the associated defence mechanisms can reveal targets for pharmacological intervention that may become the first steps towards clinically viable treatment strategies.
Read more articles from the symposium: Amyloid - a multifaceted player in human health and disease.
