Affiliation:
1. Escuela de Tecnología Médica Universidad Andrés Bello Echaurren 183 8370071 Laboratorio Catem V. Santiago Chile
2. Departamento de Física Universidad de Santiago Avenida Ecuador 3493 9170124 Santiago Chile
3. Center for Soft Matter Research, SMAT−C Usach, Avenida Bernardo O'Higgins 3363 Estación Central Santiago Chile
4. Laboratorio de Química Supramolecular y Fotobiología Departamento de Química Física Pontificia Universidad Católica de Chile Macul 7820436 Santiago Chile
Abstract
AbstractTau and α‐synuclein are proteins involved in pathologies known as tauopathies and synucleinopathies, respectively. Moreover, evidence shows that there is a crosstalk between them as is seen in the brains of individuals with sporadic neurodegenerative disorders. Based on that, we present data showing that the hydrophobic α‐peptide 71VTGVTAVAQKTV82 induces the aggregation of the full‐length tau fragment in the absence of heparin assessed by ThT. Moreover, AFM images reveal the presence of straight filaments and amorphous aggregates of full‐length tau in the presence of the α‐peptide. Additionally, ITC experiments showed the interaction of the α‐peptide with tau full‐length (441 amino acids),4R (amino acids from 244 to 369), and both hexapeptides 275VQIINK280 and 306VQIVYK311 through hydrophobic interactions. The Raman spectroscopy spectra showed conformational changes in the Amide region in the aggregates formed with full‐length tau and α‐syn peptide. Furthermore, the incubation of extracellular aggregates with N2a cells showed morphological differences in the cellular body and the nucleus suggesting cell death. Moreover,, the incubation of different types of aggregates in cell culture provokes the release of Lactate dehydrogenase (LDH). Altogether, we found that α‐synuclein peptide can drive the aggregation of full‐length tau‐provoking morphological and structural changes evoking cytotoxic effects.