• Claudia Capitini, Giulia Fani, Mirella Vivoli Vega, Amanda Penco, Claudio Canale, Lisa D Cabrita, Martino Calamai, John Christodoulou, Annalisa Relini, and Fabrizio Chiti.
• Section of Biochemistry, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
• Amyloid. 2021 Mar 1; 28 (1): 56-65.

AbstractAccumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Such inclusions have variably been described as amorphous aggregates or more structured deposits having amyloid properties. Here we have purified full-length TDP-43 (FL TDP-43) and its C-terminal domain (Ct TDP-43) to investigate the morphological, structural and tinctorial features of aggregates formed in vitro by them at pH 7.4 and 37 °C. AFM images indicate that both protein variants show a tendency to form filaments. Moreover, we show that both FL TDP-43 and Ct TDP-43 filaments possess a largely disordered secondary structure, as ascertained by far-UV circular dichroism and Fourier transform infra-red spectroscopy, do not bind Congo red and induce a very weak increase of thioflavin T fluorescence, indicating the absence of a clear amyloid-like signature.

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