Gabriel F Martins, N Galamba
Protein aggregation is implicated in multiple diseases, so-called proteinopathies, ranging from neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease (PD) to type 2 diabetes mellitus and sickle cell disease (SCD). The structure of the protein aggregates and the kinetics and mechanisms of aggregation have been the object of intense research over the years toward the development of therapeutic routes, including the design of aggregation inhibitors. Nonetheless, the rational design of drugs targeting aggregation inhibition remains a challenging endeavor because of multiple, disease-specific factors, including an incomplete understanding of protein function, the multitude of toxic and non-toxic protein aggregates, the lack of specific drug binding targets, discrepant action mechanisms of aggregation inhibitors, or a low selectivity, specificity, and/or drug potency, reflected in the high concentrations required for some inhibitors to be effective...
May 9, 2023: Critical Reviews in Biochemistry and Molecular Biology