Amyloid-Like Aggregation in Diseases and Biomaterials: Osmosis of Structural Information

Abstract

The discovery that the polypeptide chain has a remarkable and intrinsic propensity to form amyloid-like aggregates endowed with an extraordinary stability is one of the most relevant breakthroughs of the last decades in both protein/peptide chemistry and structural biology. This observation has fundamental implications, as the formation of these assemblies is systematically associated with the insurgence of severe neurodegenerative diseases. Although the ability of proteins to form aggregates rich in cross-β structure has been highlighted by recent studies of structural biology, the determination of the underlying atomic models has required immense efforts and inventiveness. Interestingly, the progressive molecular and structural characterization of these assemblies has opened new perspectives in apparently unrelated fields. Indeed, the self-assembling through the cross-β structure has been exploited to generate innovative biomaterials endowed with promising mechanical and spectroscopic properties. Therefore, this structural motif has become the fil rouge connecting these diversified research areas. In the present review, we report a chronological recapitulation, also performing a survey of the structural content of the Protein Data Bank, of the milestones achieved over the years in the characterization of cross-β assemblies involved in the insurgence of neurodegenerative diseases. A particular emphasis is given to the very recent successful elucidation of amyloid-like aggregates characterized by remarkable molecular and structural complexities. We also review the state of the art of the structural characterization of cross-β based biomaterials by highlighting the benefits of the osmosis of information between these two research areas. Finally, we underline the new promising perspectives that recent successful characterizations of disease-related amyloid-like assemblies can open in the biomaterial field.

Members of the GADD45 Protein Family Show Distinct Propensities to form Toxic Amyloid-Like Aggregates in Physiological Conditions

“…Moreover, it was found that significant portions of proteins are intrinsically disordered, and operate dynamically [ 19 ]. Finally, it has been shown that polypeptide chains have an intrinsic and unexpectedly strong propensity to self-assemble in misfolded states in which they assume a cross-β structure that is characteristic of amyloid aggregates [ 20 , 21 ]. In this scenario, here we performed a comparative biophysical characterization of the three members of the GADD45 protein family that are involved in a myriad of diversified biological processes.…”

Repair of Peripheral Nerve Injury Using Hydrogels Based on Self-Assembled Peptides

“…The specific three-dimensional structure depends on the different connection modes between peptides, including hydrogen bonding, electrostatic force hydrophobicity, and π-π interaction. In addition, β-rich structures provided important information for self-assembling peptides [34].…”

Amyloids as Building Blocks for Macroscopic Functional Materials: Designs, Applications and Challenges

“…These attractive properties of amyloid fibrils have inspired the development of various artificial materials for applications in sensors [ 31 ], medicines [ 32 , 33 ], fabrics [ 34 , 35 ], and other functional materials [ 36 , 37 , 38 ]. The use of amyloid in nanomaterials has been extensively reviewed previously [ 20 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. This review focuses on recent advances in engineering amyloids peptides or proteins as functional materials in macroscopic scales.…”