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Biochemistry. 2008 Feb 19;47(7):2181-9. doi: 10.1021/bi701322g. Epub 2008 Jan 19.

Hofmeister salts and potential therapeutic compounds accelerate in vitro fibril formation of the N-terminal domain of PABPN1 containing a disease-causing alanine extension.

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Institute for Biochemistry and Biotechnology of the Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120 Halle, Germany.

Erratum in

  • Biochemistry. 2008 Oct 7;47(40):10827.


The analysis of modulation of fibril formation helps to understand the mechanism of fibrillation processes besides opening routes for therapeutic intervention. Fibril formation was investigated with the N-terminal domain of the nuclear poly-A binding protein PABPN1, a protein in which mutation-based alanine extensions lead to the disease oculopharyngeal muscular dystrophy (OPMD). The disease is characterized by fibrillar inclusions consisting mainly of PABPN1. A systematic modulation of fibril formation kinetics was studied with trifluoroethanol, inorganic salts, low molecular weight organic substances, a poly-alanine peptide and anti-amyloidogenic compounds. Anions with salting out properties at high molar concentrations, poly-ethylene glycol and the poly-alanine peptide enhanced fibril formation rates. The effect of l-arginine on fibrillation rates depended on the counterion. Doxycycline and trehalose, compounds that have been found to mitigate OPMD symptoms in animal models, surprisingly accelerated fibril formation. Our results suggest that in the case of salts, primarily the salting out effects rather than electrostatic effects modulate fibril formation. The unexpected acceleration of fibril formation by trehalose and doxycycline questions the general view that these compounds per se impair fibril formation.

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