The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products--A Study Using Aloin and Insulin

PloS One
Eva S LobbensMarco van de Weert

Abstract

Protein fibrillation is the pathological hallmark of several neurodegenerative diseases and also complicates the manufacturing and use of protein drugs. As a case study, the inhibitory activity of the natural compound aloin against insulin fibrillation was investigated. Based on Thioflavin T assays, high-performance liquid chromatography and transmission electron microscopy it was found that a degradation product of aloin, formed over weeks of storage, was able to significantly inhibit insulin fibrillation. The activity of the stored aloin was significantly reduced in the presence of small amounts of sodium azide or ascorbic acid, suggesting the active compound to be an oxidation product. A high-performance liquid chromatography method and a liquid chromatography-mass spectrometry method were developed to investigate the degradation products in the aged aloin solution. We found that the major compounds in the solution were aloin A and aloin B. In addition, 10-hydroxy aloin and elgonica dimers were detected in smaller amounts. The identified compounds were isolated and tested for activity by means of Thioflavin T assays, but no activity was observed. Thus, the actual fibrillation inhibitor is an as yet unidentified and potential...Continue Reading

References

Sep 2, 1999·Trends in Biochemical Sciences·C M Dobson
Jan 11, 2003·Free Radical Biology & Medicine·Wayne G WamerDaniel E Falvey
Apr 21, 2004·The Journal of Biological Chemistry·Min ZhuAnthony L Fink
Nov 24, 2004·Chemistry & Biology·Jie LiAnthony L Fink
Jan 5, 2005·Journal of Structural Biology·M R H KrebsA M Donald
Apr 7, 2006·Protein Science : a Publication of the Protein Society·Todd J Gibson, Regina M Murphy
Jul 27, 2006·Biochemistry·Dong-Pyo HongAnthony L Fink
Feb 10, 2007·Journal of Structural Biology·Minna GroenningFlemming S Jørgensen
Aug 8, 2007·Journal of Structural Biology·Minna GroenningSven Frokjaer
Mar 4, 2008·The Journal of Physical Chemistry. B·Vito FoderàMaurizio Leone
Jun 23, 2009·Current Protein & Peptide Science·M GroenningB Vestergaard
Oct 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Magdalena I IvanovaDavid Eisenberg
Mar 2, 2010·Internal Medicine·Yasuyoshi ShikamaSoroku Yagihashi
Mar 25, 2010·Pharmaceutical Research·Tue RasmussenWim Jiskoot
Oct 11, 2011·Colloids and Surfaces. B, Biointerfaces·Michael I SmithAthene M Donald
Aug 29, 2012·Future Medicinal Chemistry·Laurent CalculBill J Baker
Apr 25, 2013·Journal of the American Chemical Society·Fernando L PalhanoJeffery W Kelly
Jun 15, 2013·International Journal of Molecular Sciences·Massimo Stefani, Stefania Rigacci
Jun 20, 2013·International Journal of Biological Macromolecules·Rahim AminiSeifollah Bahramikia

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR

Software Mentioned

Matlab
Topspin

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.