Interaction between tau and alpha-synuclein proteins is impaired in the presence of P301L tau mutation

Abstract

Deposits of tau and alpha-synuclein are hallmarks of distinct neurodegenerative diseases: tauopathies and alpha-synucleinopathies. Affinity chromatography experiments demonstrated a direct binding of the two proteins, and alpha-synuclein was shown to induce fibrillization of tau. Here, we verify the presence of this physical interaction by using different cellular systems. This binding was abolished by the most common tau mutation (P301L) associated with frontotemporal dementia. We restored the impaired interaction by inducing heat shock proteins 70 and 90. In addition, we show that P301L tau mutation strongly affects tau and alpha-synuclein neuronal distribution.