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Merck
CN

Hemin as a generic and potent protein misfolding inhibitor.

Biochemical and biophysical research communications (2014-12-03)
Yanqin Liu, John A Carver, Lam H Ho, Abigail K Elias, Ian F Musgrave, Tara L Pukala
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
DL-Dithiothreitol, ≥99.0% (RT)
Sigma-Aldrich
DL-Dithiothreitol, BioUltra, Molecular Biology, ≥99.5% (RT)
Sigma-Aldrich
Thioflavin T, used as stain for amyloid
Sigma-Aldrich
DL-Dithiothreitol, suitable for electrophoresis, ≥99%
Sigma-Aldrich
DL-Dithiothreitol, BioXtra, ≥99.0% (titration)
Sigma-Aldrich
DL-Dithiothreitol, Molecular Biology, ≥98% (HPLC), ≥99% (titration)
Sigma-Aldrich
DL-Dithiothreitol, ≥98% (HPLC), ≥99.0% (titration)
Sigma-Aldrich
DL-Dithiothreitol, Vetec, reagent grade, 98%
Sigma-Aldrich
Ammonium hydroxide solution, BioUltra, ~1 M NH3 in H2O (T)
Sigma-Aldrich
Ammonium hydroxide solution, ACS reagent, 28.0-30.0% NH3 basis
Sigma-Aldrich
Ammonium hydroxide solution, puriss. p.a., reag. ISO, reag. Ph. Eur., ~25% NH3 basis
Sigma-Aldrich
Ammonium hydroxide solution, puriss. p.a. plus, ≥25% NH3 in H2O
Sigma-Aldrich
Ammonium hydroxide solution, puriss., 30-33% NH3 in H2O
Sigma-Aldrich
Ammonium hydroxide solution, puriss., meets analytical specification of Ph. Eur., 25-30% NH3 basis
Sigma-Aldrich
Ammonium hydroxide solution, 28% NH3 in H2O, ≥99.99% trace metals basis