Theoretical Investigation of the Inhibitory Mechanism of Norepinephrine on hIAPP Amyloid Aggregation and the Destabilization of Protofibrils.

The Journal of Physical Chemistry. B
Rituparna Roy, Sandip Paul

Abstract

The search for an appropriate drug to completely eradicate type II diabetes (T2D), a metabolic disorder from which over 40 million people suffer worldwide, has not yet led to any satisfactory result. The misfolding of human islet amyloid polypeptide (hIAPP) into toxic oligomers is a pathogenic feature of this disease, due to which the prevention of hIAPP aggregation is considered the rational approach to combat T2D. Hence, we study the role of a catecholamine, norepinephrine, on the amyloid aggregation of hIAPP, which has previously displayed inhibitory effect on amyloid-β aggregation. Via all-atom molecular dynamics simulations, we observe that norepinephrine can not only inhibit the aggregation of hIAPP but also partially disassemble the preformed fibrils. For comparison, the influence of two other molecules (aspirin and benzimidazole, both of which have previously reported to have no inhibitory impact on hIAPP aggregation) is also analyzed. We observe that the conformational preference of hIAPP changes from a β-sheet conformation to a disordered state when norepinephrine is added to the peptides. However, no such effect is observed in the presence of aspirin or benzimidazole. In-depth investigation reveals that the β-sheets ...Continue Reading

References

Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P WestermarkC Betsholtz
Jan 1, 1994·Journal of Cellular Biochemistry·R A PittnerT J Rink
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jan 5, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ehud Gazit
Apr 7, 2004·Cell·Charles F MurchisonSteven A Thomas
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Jul 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Arjan QuistRatnesh Lal
Dec 8, 2005·Biochemistry·Andisheh Abedini, Daniel P Raleigh
Feb 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Li-Mei YanAphrodite Kapurniotu
Jun 8, 2006·Annual Review of Biochemistry·Fabrizio Chiti, Christopher M Dobson
Mar 4, 2008·Endocrine Reviews·Leena HaatajaPeter C Butler
Jul 3, 2008·The Journal of Physical Chemistry. B·In Suk Joung, Thomas E Cheatham
Oct 28, 2008·Neurobiology of Aging·Judith MiklossyPatrick L McGeer
Nov 8, 2008·Biochemistry·Ravi Prakash Reddy NangaAyyalusamy Ramamoorthy
Jan 24, 2009·Chembiochem : a European Journal of Chemical Biology·Rajesh MishraRoland Winter
Feb 21, 2009·Journal of Computational Chemistry·L MartínezJ M Martínez
Jan 1, 2008·Experimental Diabetes Research·Arne AnderssonPer Westermark
Dec 3, 2009·Journal of the American Chemical Society·Nicholas F DupuisMichael T Bowers
Dec 19, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·C Cabaleiro-LagoS Linse
Jul 31, 2010·Chembiochem : a European Journal of Chemical Biology·Silvia ScalisiCarmelo La Rosa
Apr 27, 2011·Journal of the American Chemical Society·Nicholas F DupuisMichael T Bowers
Jul 12, 2011·Physiological Reviews·Per WestermarkGunilla T Westermark
Sep 29, 2011·Accounts of Chemical Research·Jeffrey R BrenderAyyalusamy Ramamoorthy
Mar 1, 2012·Biochemical and Biophysical Research Communications·Biao ChengKun Huang
Mar 23, 2012·The Journal of Physical Chemistry. B·Aliya O KasimovaMichael Möller
Sep 6, 2012·Biophysical Journal·Michele F M SciaccaAyyalusamy Ramamoorthy
Dec 22, 2012·Biochemistry·Ling-Hsien Tu, Daniel P Raleigh

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Citations

Jan 28, 2021·Physical Chemistry Chemical Physics : PCCP·Saikat Pal, Sandip Paul
Jun 30, 2021·Physical Chemistry Chemical Physics : PCCP·Srijita Paul, Sandip Paul
Jul 10, 2021·The Journal of Physical Chemistry. B·Susmita Sarkar, Jagannath Mondal

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