Abstract
Biomolecular self-assembly is a fundamental process in all organisms. As primary components of the life molecular machinery, proteins have a vast array of resources available to them for self-assembly in a functional structure. Protein self-assembly, however, can also occur in an aberrant way, giving rise to non-native aggregated structures responsible for severe, progressive human diseases that have a serious social impact. Different neurodegenerative disorders, like Huntington’s, Alzheimer’s, and spongiform encephalopathy diseases, have in common the presence of insoluble protein aggregates, generally termed “amyloid,” that share several physicochemical features: a fibrillar morphology, a predominantly beta-sheet secondary structure, birefringence upon staining with the dye Congo red, insolubility in common solvents and detergents, and protease resistance. Conformational constrains, hydrophobic and stacking interactions can play a key role in the fibrillogenesis process and protein–protein and peptide–peptide interactions—resulting in self-assembly phenomena of peptides yielding fibrils—that can be modulated and influenced by natural biomolecules. Small organic molecules, which possess both hydrophilic and hydrophobic moieties able to bind to peptide/protein molecules through hydrogen bonds and hydrophobic and aromatic interactions, are potential candidates against amyloidogenesis. In this review some significant case examples will be critically discussed.
Highlights
Several natural molecules derived from animals, plants, fungi, bacteria and other organisms show an extraordinary structural diversity, as well as a broad range of biological activities
It is worthwhile emphasizing that amyloid fibrils, involved in different pathologies, are surprisingly similar in their morphology and structural properties, even though they originate from quite different proteins with different amino acids sequences, folded in very diverse and peculiar native structures [22]
In contrast to what has been hypothesized before, the protein native state may be only metastable with respect to amyloid formation, because of the high kinetic barriers associated with the in vivo self-assembly of polypeptide chains [27]
Summary
Several natural molecules derived from animals, plants, fungi, bacteria and other organisms show an extraordinary structural diversity, as well as a broad range of biological activities. They represent one of the major sources of therapeutic remedies and important tools for developing innovative drugs. Natural compounds have been designed by evolution to have functional groups well-fitting biomolecular frameworks. They can be considered privileged structures able to interact with biological membranes and macromolecules, mostly proteins [1]. The importance of protein misfolding and aggregation in amyloid-related diseases will be dealt with, and some of the most recent findings on the effects of natural molecules on these processes will be discussed
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