The intrinsically disordered tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and other human tauopathies. Abnormal post-translational modifications of tau, such as truncation, are causally involved in the onset/development of these neurodegenerative diseases. In this context, the AD-relevant N-terminal fragment mapping between 26 and 44 amino acids of protein (tau26-44) is interesting, being endowed with potent neurotoxic effects in vitro and in vivo. However, the understanding of the mechanism(s) of tau26-44 toxicity is a challenging task because, similarly to the full-length tau, it does not have a unique 3D structure but exists as dynamic ensemble of conformations. Here we use Atomic Force Spectroscopy, Small Angle X-ray Scattering and Molecular Dynamics simulation to gather structural and functional information on the tau26-44. We highlight the presence, the type and the location of its temporary secondary structures and we unveil the occurrence of relevant transient tertiary conformations that could contribute to tau26-44 toxicity. Data are compared with those obtained on the biologically-inactive, reverse-sequence (tau44-26 peptide) which has the same mass, charge, aminoacidic composition as well as the same overall unfolded character of tau26-44.

Perini, G., Ciasca, G., Minelli, E., Papi, M., Palmieri, V., Maulucci, G., Nardini, M., Latina, V., Corsetti, V., Florenzano, F., Calissano, P., De Spirito, M., Amadoro, G., Dynamic structural determinants underlie the neurotoxicity of the N-terminal tau 26-44 peptide in Alzheimer's disease and other human tauopathies, <<INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES>>, 2019; 141 (N/A): 278-289. [doi:10.1016/j.ijbiomac.2019.08.220] [http://hdl.handle.net/10807/155256]

Dynamic structural determinants underlie the neurotoxicity of the N-terminal tau 26-44 peptide in Alzheimer's disease and other human tauopathies

Perini G.
Primo
;
Ciasca G.
;
Minelli E.;Papi M.;Palmieri V.;Maulucci G.;Nardini M.;De Spirito M.
Penultimo
;
2019

Abstract

The intrinsically disordered tau protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and other human tauopathies. Abnormal post-translational modifications of tau, such as truncation, are causally involved in the onset/development of these neurodegenerative diseases. In this context, the AD-relevant N-terminal fragment mapping between 26 and 44 amino acids of protein (tau26-44) is interesting, being endowed with potent neurotoxic effects in vitro and in vivo. However, the understanding of the mechanism(s) of tau26-44 toxicity is a challenging task because, similarly to the full-length tau, it does not have a unique 3D structure but exists as dynamic ensemble of conformations. Here we use Atomic Force Spectroscopy, Small Angle X-ray Scattering and Molecular Dynamics simulation to gather structural and functional information on the tau26-44. We highlight the presence, the type and the location of its temporary secondary structures and we unveil the occurrence of relevant transient tertiary conformations that could contribute to tau26-44 toxicity. Data are compared with those obtained on the biologically-inactive, reverse-sequence (tau44-26 peptide) which has the same mass, charge, aminoacidic composition as well as the same overall unfolded character of tau26-44.
Inglese
Perini, G., Ciasca, G., Minelli, E., Papi, M., Palmieri, V., Maulucci, G., Nardini, M., Latina, V., Corsetti, V., Florenzano, F., Calissano, P., De Spirito, M., Amadoro, G., Dynamic structural determinants underlie the neurotoxicity of the N-terminal tau 26-44 peptide in Alzheimer's disease and other human tauopathies, <>, 2019; 141 (N/A): 278-289. [doi:10.1016/j.ijbiomac.2019.08.220] [http://hdl.handle.net/10807/155256]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/155256
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