ABSTRACT

Protein aggregation proceeds through a twostep process that starts with nucleation and proceeds to fibrillization (Figure 1.1). The process of protein aggregation can be understood by considering the process of crystallization. Crystallization exhibits a strong lag phase during which nucleation occurs. Nucleation is the rate-limiting step in crystallization. Once nucleation occurs and crystal niduses are generated, crystal formation occurs rapidly. Protein aggregation exhibits similar phenomena. Protein aggregation begins slowly and exhibits a strong lag phase. During the lag phase, small protofibrils form. Once sufficient numbers of protofibrils have formed, the fibrils

begin to coalesce to form large fibrils, and the rate of protein aggregation increases greatly (Figure 1.1).