Peptides NAP and SAL attenuate human tau granular-shaped oligomers in vitro and in SH-SY5Y cells

Abstract

Accumulation of human tau protein in the central nervous system is an outstanding feature of Alzheimer's Diseases and other tauopathies. Among the aggregate species, granular-shaped oligomers are recently reported as toxic species and associated with neuronal loss. Many interests have been focused on the reducing of these neurotoxic oligomers in tauopathies. It has been approved that peptides NAP (NAPVSIPQ) and SAL (SALLRSIPA), snipped from activity-dependent neurotrophic protein (ADNP) and activity-dependent neurotrophic factor (ADNF), protect brain against a wide range of toxins in neurodegenerative models. The neuroprotection mechanisms of NAP and SAL are under investigation. We report here that the aggregation pathway of human tau protein, in the presence of NAP or SAL, could be affected and moved toward the less granular-shaped species. Fluorophore binding assays, kinetic parameters and circular dichroism records, showed the presence of unusual aggregated species upon treatment with NAP or SAL, as well as hydrophobicity studies. Also, sizing and morphological investigation of aggregates, using dynamic scattered light and Atomic Force Microscopy, elucidated a significant reduction of granular-shaped oligomers under 50nm. Furthermore, immunospecific detection of oligomers in SH-SY5Y cell line, using flow cytometric assessment supported our results. We conclude that one of the possible mechanisms of neuronal protection by NAP or SAL could be the attenuation of granular-shaped oligomeric tau under stress condition.