Determination of critical nucleation number for a single nucleation amyloid-β aggregation model

Mathematical Biosciences
Preetam GhoshVijayaraghavan Rangachari

Abstract

Aggregates of amyloid-β (Aβ) peptide are known to be the key pathological agents in Alzheimer disease (AD). Aβ aggregates to form large, insoluble fibrils that deposit as senile plaques in AD brains. The process of aggregation is nucleation-dependent in which the formation of a nucleus is the rate-limiting step, and controls the physiochemical fate of the aggregates formed. Therefore, understanding the properties of nucleus and pre-nucleation events will be significant in reducing the existing knowledge-gap in AD pathogenesis. In this report, we have determined the plausible range of critical nucleation number (n(*)), the number of monomers associated within the nucleus for a homogenous aggregation model with single unique nucleation event, by two independent methods: A reduced-order stability analysis and ordinary differential equation based numerical analysis, supported by experimental biophysics. The results establish that the most likely range of n(*) is between 7 and 14 and within, this range, n(*) = 12 closely supports the experimental data. These numbers are in agreement with those previously reported, and importantly, the report establishes a new modeling framework using two independent approaches towards a convergent s...Continue Reading

References

Sep 24, 1993·Annals of the New York Academy of Sciences·J T JarrettP T Lansbury
Feb 1, 1997·Chemistry & Biology·J D HarperP T Lansbury
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·A LomakinG B Benedek
Aug 29, 1997·The Journal of Biological Chemistry·D M WalshD B Teplow
May 10, 2000·Journal of Molecular Biology·H K BlackleyM J Wilkinson
Aug 15, 2000·Journal of Structural Biology·R M Murphy, M M Pallitto
Aug 15, 2000·Journal of Structural Biology·J McLaurinP E Fraser
Jul 16, 2002·Annual Review of Biomedical Engineering·Regina M Murphy
Aug 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Songming ChenRonald Wetzel
Nov 5, 2002·Annual Review of Pharmacology and Toxicology·Dennis J Selkoe, Dale Schenk
May 3, 2003·Current Opinion in Structural Biology·D ThirumalaiR I Dima
Jun 9, 2004·Protein and Peptide Letters·Dominic M Walsh, Dennis J Selkoe
Aug 6, 2004·Nature·Mark P Mattson
Feb 28, 2007·Biophysical Journal·Chuang-Chung LeeGregory J McRae
Dec 17, 2008·Biochimica Et Biophysica Acta·Aimee M MorrisRichard G Finke
Feb 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kanchan Garai, Carl Frieden
May 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Samuel I A CohenTuomas P J Knowles
Dec 3, 2014·Journal of Molecular Biology·Frank A Ferrone
Dec 3, 2014·Proceedings of the National Academy of Sciences of the United States of America·Anđela ŠarićDaan Frenkel
Jan 15, 2015·The Journal of Physical Chemistry. B·Volodymyr V ShvadchakVinod Subramaniam

❮ Previous
Next ❯

Citations

Jan 18, 2017·Scientific Reports·Dexter N DeanVijayaraghavan Rangachari
Sep 6, 2017·Scientific Reports·Pratip RanaPreetam Ghosh
Aug 24, 2017·Protein Science : a Publication of the Protein Society·Bartosz NizynskiKrzysztof Nieznanski
Dec 6, 2019·Archives of Biochemistry and Biophysics·Vali AkbariReza Khodarahmi
Feb 8, 2018·Biophysical Journal·Dexter N DeanVijayaraghavan Rangachari
Oct 30, 2019·ACS Chemical Neuroscience·Viet Hoang ManJunmei Wang
Jun 13, 2019·Biochemistry·Albert W PilkingtonJustin Legleiter
Aug 1, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Michael J Lucas, Benjamin K Keitz
Nov 13, 2021·Journal of Neurochemistry·Martyna M MatuszykStephen B Wharton

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.