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Title: Hemin as a generic and potent protein misfolding inhibitor

Abstract

Highlights: • Hemin prevents Aβ42, α-synuclein and RCM-κ-casein forming amyloid fibrils. • Hemin inhibits the β-sheet structure formation of Aβ42. • Hemin reduces the cell toxicity caused by fibrillar Aβ42. • Hemin dissociates partially formed Aβ42 fibrils. • Hemin prevents amorphous aggregation by ADH, catalase and γs-crystallin. - Abstract: Protein misfolding causes serious biological malfunction, resulting in diseases including Alzheimer’s disease, Parkinson’s disease and cataract. Molecules which inhibit protein misfolding are a promising avenue to explore as therapeutics for the treatment of these diseases. In the present study, thioflavin T fluorescence and transmission electron microscopy experiments demonstrated that hemin prevents amyloid fibril formation of kappa-casein, amyloid beta peptide and α-synuclein by blocking β-sheet structure assembly which is essential in fibril aggregation. Further, inhibition of fibril formation by hemin significantly reduces the cytotoxicity caused by fibrillar amyloid beta peptide in vitro. Interestingly, hemin degrades partially formed amyloid fibrils and prevents further aggregation to mature fibrils. Light scattering assay results revealed that hemin also prevents protein amorphous aggregation of alcohol dehydrogenase, catalase and γs-crystallin. In summary, hemin is a potent agent which generically stabilises proteins against aggregation, and has potential as a key molecule for the development of therapeutics for protein misfoldingmore » diseases.« less

Authors:
 [1];  [2]; ;  [1];  [3]
  1. School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005 (Australia)
  2. Discipline of Pharmacology, The University of Adelaide, Adelaide, SA 5005 (Australia)
  3. Research School of Chemistry, The Australian National University, Canberra, ACT 0200 (Australia)
Publication Date:
OSTI Identifier:
22416830
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 454; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALCOHOL DEHYDROGENASE; BROMIDES; CASEIN; CATALASE; CATARACTS; CYANIDES; DICHROISM; FLUORESCENCE; HEME; IN VITRO; INHIBITION; LIGHT SCATTERING; MOLECULES; NERVOUS SYSTEM DISEASES; PEPTIDES; TOXICITY; TRANSMISSION ELECTRON MICROSCOPY

Citation Formats

Liu, Yanqin, Carver, John A., Ho, Lam H., Elias, Abigail K., Musgrave, Ian F., and Pukala, Tara L., E-mail: tara.pukala@adelaide.edu.au. Hemin as a generic and potent protein misfolding inhibitor. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.10.062.
Liu, Yanqin, Carver, John A., Ho, Lam H., Elias, Abigail K., Musgrave, Ian F., & Pukala, Tara L., E-mail: tara.pukala@adelaide.edu.au. Hemin as a generic and potent protein misfolding inhibitor. United States. doi:10.1016/J.BBRC.2014.10.062.
Liu, Yanqin, Carver, John A., Ho, Lam H., Elias, Abigail K., Musgrave, Ian F., and Pukala, Tara L., E-mail: tara.pukala@adelaide.edu.au. Fri . "Hemin as a generic and potent protein misfolding inhibitor". United States. doi:10.1016/J.BBRC.2014.10.062.
@article{osti_22416830,
title = {Hemin as a generic and potent protein misfolding inhibitor},
author = {Liu, Yanqin and Carver, John A. and Ho, Lam H. and Elias, Abigail K. and Musgrave, Ian F. and Pukala, Tara L., E-mail: tara.pukala@adelaide.edu.au},
abstractNote = {Highlights: • Hemin prevents Aβ42, α-synuclein and RCM-κ-casein forming amyloid fibrils. • Hemin inhibits the β-sheet structure formation of Aβ42. • Hemin reduces the cell toxicity caused by fibrillar Aβ42. • Hemin dissociates partially formed Aβ42 fibrils. • Hemin prevents amorphous aggregation by ADH, catalase and γs-crystallin. - Abstract: Protein misfolding causes serious biological malfunction, resulting in diseases including Alzheimer’s disease, Parkinson’s disease and cataract. Molecules which inhibit protein misfolding are a promising avenue to explore as therapeutics for the treatment of these diseases. In the present study, thioflavin T fluorescence and transmission electron microscopy experiments demonstrated that hemin prevents amyloid fibril formation of kappa-casein, amyloid beta peptide and α-synuclein by blocking β-sheet structure assembly which is essential in fibril aggregation. Further, inhibition of fibril formation by hemin significantly reduces the cytotoxicity caused by fibrillar amyloid beta peptide in vitro. Interestingly, hemin degrades partially formed amyloid fibrils and prevents further aggregation to mature fibrils. Light scattering assay results revealed that hemin also prevents protein amorphous aggregation of alcohol dehydrogenase, catalase and γs-crystallin. In summary, hemin is a potent agent which generically stabilises proteins against aggregation, and has potential as a key molecule for the development of therapeutics for protein misfolding diseases.},
doi = {10.1016/J.BBRC.2014.10.062},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 454,
place = {United States},
year = {2014},
month = {11}
}