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Effect of trehalose and ceftriaxone on the stability of aggregating-prone tau peptide containing PHF6* sequence: an SRCD study

DOI: 10.3390/ijms23062932 DOI Help

Authors: Claudia Honisch (Institute of Biomolecular Chemistry of CNR; University of Padua) , Federica Torni (Institute of Biomolecular Chemistry of CNR) , Rohanah Hussain (Diamond Light Source) , Paolo Ruzza (Institute of Biomolecular Chemistry of CNR) , Giuliano Siligardi (Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: International Journal Of Molecular Sciences , VOL 23

State: Published (Approved)
Published: March 2022
Diamond Proposal Number(s): 23764 , 25489

Open Access Open Access

Abstract: The tau protein, a soluble protein associated with microtubules, which is involved in the assembly and stabilization of cytoskeletal elements, was found to form neurofibrillary tangles in different neurodegenerative diseases. Insoluble tau aggregates were observed to be organized in paired helical filaments (PHFs) and straight filaments (SFs). Recently, two small sequences (306–311 and 275–280) in the microtubule-binding region (MTBR), named PHF6 and PHF6*, respectively, were found to be essential for tau aggregation. Since a possible therapeutic approach consists of impairing amyloid formation either by stabilizing the native proteins or reducing the level of amyloid precursors, here we use synchrotron radiation circular dichroism (SRCD) at Diamond B23 beamline to evaluate the inhibitory effects of two small molecules, trehalose and ceftriaxone, against the aggregation of a small peptide containing the PHF6* sequence. Our results indicate that both these molecules, ceftriaxone and trehalose, increased the stability of the peptide toward aggregation, in particular that induced by heparin. With trehalose being present in many fruits, vegetables, algae and processed foods, these results support the need to investigate whether a diet richer in trehalose might exert a protective effect toward pathologies linked to protein misfolding.

Journal Keywords: tau protein; intrinsically disordered proteins; tauopathies; protein aggregation; trehalose; ceftriaxone; conformational stability; synchrotron radiation circular dichroism; transmission electron microscopy

Subject Areas: Biology and Bio-materials, Medicine


Instruments: B23-Circular Dichroism

Added On: 11/03/2022 09:24

Documents:
ijms-23-02932.pdf

Discipline Tags:

Neurodegenerative Diseases Health & Wellbeing Neurology Biophysics Life Sciences & Biotech

Technical Tags:

Spectroscopy Circular Dichroism (CD)