Inhibition of Aβ1-42 fibrillation by chaperonins: human Hsp60 is a stronger inhibitor than its bacterial homologue GroEL.

08:00 EDT 12th July 2019 | BioPortfolio

Summary of "Inhibition of Aβ1-42 fibrillation by chaperonins: human Hsp60 is a stronger inhibitor than its bacterial homologue GroEL."

Alzheimer's disease is a chronic neurodegenerative disease characterized by the accumulation of pathological aggregates of amyloid beta peptide. Many efforts have been focused on understanding peptide aggregation pathways and on identification of molecules able to inhibit aggregation in order to find an effective therapy. As a result, interest in neuroprotective proteins, such as molecular chaperones has increased as their normal function is to assist in protein folding, or to facilitate the disaggregation and/or clearance of abnormal aggregate proteins. Using biophysical techniques, we evaluated the effects of two chaperones, human Hsp60 and bacterial GroEL, on the fibrillogenesis of Aβ142. Both chaperonins interfere with Aβ142 aggregation, but the effect of Hsp60 is more significant and correlates with its more pronounced flexibility and stronger interaction with ANS, an indicator of hydrophobic regions. Dose-dependent ThT fluorescence kinetics and SAXS experiments reveal that Hsp60 does not change the nature of the molecular processes stochastically leading to the formation of seeds, but strongly delays them by recognition of hydrophobic sites of some peptide species crucial for triggering amyloid formation. Hsp60 reduces the initial chaotic heterogeneity of Aβ142 sample at high concentration regimes. The understanding of chaperone action in counteracting pathological aggregation could be a starting point for potential new therapeutic strategies against neurodegenerative diseases.


Journal Details

This article was published in the following journal.

Name: ACS chemical neuroscience
ISSN: 1948-7193


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Medical and Biotech [MESH] Definitions

A subcategory of chaperonins found in ARCHAEA and the CYTOSOL of eukaryotic cells. Group II chaperonins form a barrel-shaped macromolecular structure that is distinct from GROUP I CHAPERONINS in that it does not utilize a separate lid like structure to enclose proteins.

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A subcategory of chaperonins found in MITOCHONDRIA; CHLOROPLASTS; and BACTERIA. Group I chaperonins form into a barrel-shaped macromolecular structure that is enclosed by a separate lid-like protein component.

A THROMBIN inhibitor which acts by binding and blocking thrombogenic activity and the prevention of thrombus formation. It is used to reduce the risk of stroke and systemic EMBOLISM in patients with nonvalvular atrial fibrillation.

A high-molecular-weight protein (approximately 22,500) containing 198 amino acid residues. It is a strong inhibitor of trypsin and human plasmin.

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