Transthyretin (TTR) aggregation has been characterized to be responsible for several amyloid diseases. Fourier transform infrared (FTIR) spectroscopy, fluorescence, and atomic force microscopy (AFM) are used to investigate secondary structure changes in transthyretin, induced upon thermal denaturation and interaction with pentobarbital. Spectral analysis revealed a strong static quenching of the intrinsic fluorescence of TTR by pentobarbital with a binding constant (K) estimated at . Fourier self-deconvolution (FSD) technique is used to evaluates intensity changes in the spectra of the component bands in the amide I and amide II regions due to the changes in pentobarbital concentration in the protein complex. The increases of the relative intensities of the peaks at 1614？cm？1 and 1507？cm？1 are due to the increase of pentobarbital concentrations which is linked to the formation of oligomers in the protein. 1. Introduction Transthyretin (TTR) is a plasma protein composed of 127-residue subunits mainly composed of β-sheet structures [1]. It is present in both human plasma and cerebrospinal fluid (CSF) with concentrations of (0.1–0.4？mg/mL) in human plasma and (0.017？mg/mL) in CSF [2]. X-ray crystal structure studies have shown that human TTR have a molecular weight of 55？kDa in a tetramer form with four identical subunits [3]. TTR is synthesized by the liver and released in the plasma, while the TTR in CSF is mostly produced by the choroid plexus [4–6]. It is considered to be the primary transporter of thyroid hormones in the form of thyroxine in the CSF and it carries retinol via interaction with the retinol-binding protein (RBP) [7]. Other additional function of TTR has been detected in the development of the central nervous system due to the high concentration during the prenatal and postnatal life [8]. Several research groups have shown cerebral TTR expression to rise during the course of experimental Alzheimer disease (AD) in mice and in response to the intake of some drug or mixtures of compounds such as gingko extracts or dietary fatty acids [9–11]. The process of transthyretin amyloidogenesis or amyloid fibril formation seems to be associated with some amyloid diseases. It is not understood precisely how TTR forms amyloids, but several biophysical studies on wild-type (WT) TTR reveals that tetramer dissociation is rate limiting for amyloidogenesis [12–14]. All amyloid diseases are characterized by misfolded proteins that undergo aggregation causing a deposition of insoluble amyloid fibrils either systemically or in specific organs as the brain
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