Amyloid Structure and Properties and Its Relation to Human Diseases

Natalia Lisitza


Amyloid – a fibrillar, cross β-sheet quaternary structure –was first discovered and associated with a great variety of human diseases (Alzheimer’s, Parkinson’s, prion, diabetes, cataracts, etc.). It is believed that the misfolding and aggregation of amyloid proteins are responsible for the appearance and progression of these diseases. Protein aggregation is a highly complex process resulting in a variety of aggregates with different structures and morphologies. Oligomeric protein aggregates (amyloid oligomers) are formed as both intermediates and final products of the aggregation process. They are believed to play an important role in many protein aggregation-related diseases, and many of them are highly cytotoxic. Due to their instability and structural heterogeneity, information about structure, mechanism of formation, and physiological effects of amyloid oligomers is sparse. Here we review the molecular properties of amyloid proteins and relate them to the pathological conditions and the appearance of various diseases. We show how the structure of the amyloid protein at different hierarchical levels (from backbone to fibrills) is representative to the pathological changes that appear at the disease and how it can be potentially be employed to monitor the disease progression. We also review the cytotoxicity of the amyloid proteins and discuss how it might be related to the structure. In conclusion, we delineate the intervention strategies that prevent amyloid formation.

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