Show simple item record

dc.contributor.authorHoore, Masoud
dc.contributor.authorKhailaie, Sahamoddin
dc.contributor.authorMontaseri, Ghazal
dc.contributor.authorMitra, Tanmay
dc.contributor.authorMeyer-Hermann, Michael
dc.date.accessioned2020-11-19T15:23:56Z
dc.date.available2020-11-19T15:23:56Z
dc.date.issued2020-07-22
dc.identifier.citationBiophys J. 2020 Aug 18;119(4):862-872. doi: 10.1016/j.bpj.2020.07.011. Epub 2020 Jul 22.en_US
dc.identifier.pmid32758420
dc.identifier.doi10.1016/j.bpj.2020.07.011
dc.identifier.urihttp://hdl.handle.net/10033/622602
dc.description.abstractDeposition of amyloid-β (Aβ) fibers in the extracellular matrix of the brain is a ubiquitous feature associated with several neurodegenerative disorders, especially Alzheimer's disease (AD). Although many of the biological aspects that contribute to the formation of Aβ plaques are well addressed at the intra- and intercellular levels in short timescales, an understanding of how Aβ fibrillization usually starts to dominate at a longer timescale despite the presence of mechanisms dedicated to Aβ clearance is still lacking. Furthermore, no existing mathematical model integrates the impact of diurnal neural activity as emanated from circadian regulation to predict disease progression due to a disruption in the sleep-wake cycle. In this study, we develop a minimal model of Aβ fibrillization to investigate the onset of AD over a long timescale. Our results suggest that the diseased state is a manifestation of a phase change of the system from soluble Aβ (sAβ) to fibrillar Aβ (fAβ) domination upon surpassing a threshold in the production rate of sAβ. By incorporating the circadian rhythm into our model, we reveal that fAβ accumulation is crucially dependent on the regulation of the sleep-wake cycle, thereby indicating the importance of good sleep hygiene in averting AD onset. We also discuss potential intervention schemes to reduce fAβ accumulation in the brain by modification of the critical sAβ production rate.en_US
dc.language.isoenen_US
dc.publisherElsevier (CellPress)en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleMathematical Model Shows How Sleep May Affect Amyloid-β Fibrillization.en_US
dc.typeArticleen_US
dc.identifier.eissn1542-0086
dc.contributor.departmentBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalBiophysical journalen_US
dc.source.volume119
dc.source.issue4
dc.source.beginpage862
dc.source.endpage872
refterms.dateFOA2020-11-19T15:23:57Z
dc.source.journaltitleBiophysical journal
dc.source.countryUnited States


Files in this item

Thumbnail
Name:
Publisher version
Thumbnail
Name:
Hoore et al.pdf
Size:
1.324Mb
Format:
PDF
Description:
Open Access article

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-ShareAlike 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International