scholarly journals The Binding of Apolipoprotein E to Oligomers and Fibrils of Amyloid-β Alters the Kinetics of Amyloid Aggregation

Biochemistry ◽  
2014 ◽  
Vol 53 (40) ◽  
pp. 6323-6331 ◽  
Author(s):  
Kanchan Garai ◽  
Philip B. Verghese ◽  
Berevan Baban ◽  
David M. Holtzman ◽  
Carl Frieden
Keyword(s):  
Apolipoprotein E ◽  
Amyloid Β ◽  
Amyloid Aggregation ◽  
Kinetics Of

scholarly journals Apolipoprotein E interacts with amyloid-β oligomers via positively cooperative multivalent binding

2018 ◽  
Author(s):  
S. Ghosh ◽  
T. B. Sil ◽  
S. Dolai ◽  
K. Garai
Keyword(s):  
Apolipoprotein E ◽  
Amyloid Β ◽  
Resonance Energy ◽  
Full Length ◽  
Aβ Oligomers ◽  
Critical Determinant ◽  
Competitive Binding Assay ◽  
Terminal Fragment ◽  
Multivalent Binding ◽  
Kinetics Of

AbstractInteraction of apolipoprotein E (apoE) isoforms with amyloid-β (Aβ) peptides is considered a critical determinant of the progression of Alzheimer’s disease. However, molecular mechanism of the apoE-Aβ interaction is poorly understood. Here we characterize the nature of the apoE-Aβ complexes and identify the region of apoE that interacts with Aβ. We have prepared three distinct fragments of apoE4, viz., the N-terminal fragment (NTF), hinge domain fragment (HDF) and C-terminal fragment (CTF) to compare its interactions with Aβ. Kinetics of aggregation of Aβ is delayed dramatically in presence of low, substoichiometric concentrations of both NTF and CTF in lipid-free, as well as, in lipidated forms. Effect of HDF is found to be small. Strong inhibition by NTF and CTF at substoichiometric concentrations indicate interactions with the ‘intermediates’ or the oligomers of Aβ. Kinetics of Forster Resonance Energy Transfer (FRET) between full-length apoE4 labeled with EDANS at positions 62, 139, 210, 247, and 276 and tetramethylrhodamine (TMR)-labeled Aβ further support involvement of multiple regions of apoE in the interactions. Since the interactions involve intermediates of Aβ quantitative evaluation of the binding affinities are not feasible. Hence we employed a competitive binding assay to examine whether the N- and C-terminal domains interact cooperatively. Addition of unlabeled full-length apoE eliminates the FRET between EDANS-NTF + EDANS-CTF and TMR-Aβ almost completely but not vice versa. Furthermore, full-length apoE but not the equimolar mixture of the fragments could displace the already bound EDANS-apoE molecules from the complexes. Therefore, binding affinity of the Aβ oligomers to the intact full-length apoE is much higher than the affinity to the domains when mixed together as fragments. Thus, our results indicate that apoE-Aβ complex formation is mediated by positively cooperative multivalent binding between the multiple sites on apoE and the oligomeric forms of Aβ.

scholarly journals Kinetics of amyloid β from deep learning

2021 ◽  
Vol 1 (1) ◽  
pp. 20-21
Author(s):  
Fanjie Meng ◽  
Hoi Sung Chung
Keyword(s):  
Deep Learning ◽  
Amyloid Β ◽  
Kinetics Of

Differential Influence of Amyloid-β on the Kinetics of Dopamine Release in the Dorsal and Ventral Striatum of Rats

2021 ◽  
Author(s):  
Valery N. Mukhin ◽  
Ivan R. Borovets ◽  
Vadim V. Sizov ◽  
Konstantin I. Pavlov ◽  
Victor M. Klimenko
Keyword(s):  
Dopamine Release ◽  
Ventral Striatum ◽  
Amyloid Β ◽  
Kinetics Of

scholarly journals Thermodynamics and kinetics of the amyloid-β peptide revealed by Markov state models based on MD data in agreement with experiment

2021 ◽  
Author(s):  
Arghadwip Paul ◽  
Suman Samantray ◽  
Marco Anteghini ◽  
Mohammed Khaled ◽  
Birgit Strodel
Keyword(s):  
Amyloid Β ◽  
Md Simulations ◽  
Amyloid Β Peptide ◽  
Intrinsically Disordered ◽  
Thermodynamics And Kinetics ◽  
Markov State ◽  
Markov State Models ◽  
State Models ◽  
Kinetics Of

The convergence of MD simulations is tested using varying measures for the intrinsically disordered amyloid-β peptide (Aβ). Markov state models show that 20–30 μs of MD is needed to reliably reproduce the thermodynamics and kinetics of Aβ.

scholarly journals Kinetics of Amyloid Aggregation: A Study of the GNNQQNY Prion Sequence

2012 ◽  
Vol 8 (11) ◽  
pp. e1002782 ◽  
Author(s):  
Jessica Nasica-Labouze ◽  
Normand Mousseau
Keyword(s):  
Amyloid Aggregation ◽  
Kinetics Of

Kinetics of apolipoprotein E binding to glycosaminoglycans

1999 ◽  
Vol 144 ◽  
pp. 108
Author(s):  
V.V. Shuvaev ◽  
I. Laffont ◽  
G. Siest
Keyword(s):  
Apolipoprotein E ◽  
Kinetics Of

Apolipoprotein E ε4 allele is associated with deposition of amyloid β-protein following head injury

1995 ◽  
Vol 1 (2) ◽  
pp. 135-137 ◽  
Author(s):  
James A.R. Nicoll ◽  
Gareth W. Roberts ◽  
David I. Graham
Keyword(s):  
Head Injury ◽  
Apolipoprotein E ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Ε4 Allele
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