Nanoimaging in protein-misfolding and -conformational diseases

Abstract

Protein misfolding and the subsequent assembly of protein molecules into aggregates of various morphologies represent common mechanisms that link a number of important human diseases, known as protein-misfolding diseases. The current list of these disorders includes (but is not limited to) numerous neurodegenerative diseases, cataracts, arthritis, medullary carcinoma of the thyroid, late-onset diabetes mellitus, symptomatic (hemodialysis-related) β2-microglobulin amyloidosis, arthritis and many other systemic, localized and familial amyloidoses. Progress in understanding protein-misfolding pathologies and in potential rational drug design aimed at the inhibition or reversal of protein aggregation depends on our ability to study the details of the misfolding process, to follow the aggregation process and to see and analyze the structure and mechanical properties of the aggregated particles. Nanoimaging provides a method to monitor the aggregation process, visualize protein aggregates and analyze their properties and provides fundamental knowledge of key factors that lead to protein misfolding and self-assembly in various protein-misfolding pathologies, therefore advancing medicine dramatically.