Effect(s) of Self‐Assembled Structures of Phenylalanine on the Amyloid‐like Fibril Formation of the Human Acidic Fibroblast Growth Factor

Abstract

Excessive concentrations of the natural aromatic amino acid, phenylalanine, is characteristic of the severe genetic abnormality known as phenylketonuria (PKU). However, the fundamental mechanism by which phenylalanine causes the disease is largely unknown. Similarly, the etiology of Alzheimer’s disease is widely debated. Previous research has found elevated levels of acidic fibroblast growth factor (FGF1), a prototypical member of the FGF superfamily of cell signaling molecules which assist in cell differentiation and proliferation, wound healing, and neurogenesis, in cerebrospinal fluid of Alzheimer’s patients. This suggests that FGF1 may exert a significant role in neuroprotection. Under certain conditions, however, FGF1 has been found to form amyloid‐like fibrils (Srisialam et al. 2003), rendering it biologically inactive. Thioflavin T fluorescence kinetics and transmission electron microscopy (TEM) data suggest the formation of higher ordered fibrillar structures by phenylalanine in vitro. Fluorescence kinetics of phenylalanine reveal a higher propensity to self‐assemble at pH 2. Seeding experiments suggest the potential of phenylalanine (at 6 mM) to inhibit fibril formation of FGF1 and the modulation of its neuroprotective activity. These data will be discussed in detail.