Key Factors Controlling Fibril Formation of Proteins

Fibril formation resulting from protein aggregation is a hallmark of a large group of neurodegenerative human diseases, including Alzheimer's disease, type 2 diabetes, amyotrophic lateral sclerosis, and Parkinson's disease, among many others. Key factors governing protein fibril formation have been identified over the past decades to elucidate various facets of misfolding and aggregation. However, surprisingly little is known about how and why fibril structure is achieved, and it remains a fundamental problem in molecular biology. In this review, we discuss the relationship between fibril formation kinetics and various characteristics, including sequence, mutations, monomer secondary structure, mechanical stability of the fibril state, aromaticity, hydrophobicity, charge, and population of fibril-prone conformations in the monomeric state.