Amyloid fibrils and soluble oligomers are two types of protein aggregates associated with neurodegeneration. Classic therapeutic strategies try to prevent the nucleation and spread of amyloid fibrils, whilst diffusible oligomers have emerged as promising drug targets affecting downstream pathogenic processes. We developed a generic protein aggregation model and validate it against measured compositions of fibrillar and non-fibrillar assemblies of ataxin-3, a protein implicated in Machado-Joseph disease. The derived analytic rate-law equations can be used to (i) identify the presence of parallel aggregation pathways and (ii) estimate the critical sizes of amyloid fibrils. The discretized population balance supporting our model is the first to quantitatively fit time-resolved measurements of size and composition of both amyloid-like and oligomeric species. The new theoretical framework can be used to screen a new class of drugs specifically targeting toxic oligomers.
[NMR paper] Water Distribution, Dynamics and Interactions with Alzheimer's ?-Amyloid Fibrils Investigated by Solid-State NMR.
Water Distribution, Dynamics and Interactions with Alzheimer's ?-Amyloid Fibrils Investigated by Solid-State NMR.
Water Distribution, Dynamics and Interactions with Alzheimer's ?-Amyloid Fibrils Investigated by Solid-State NMR.
J Am Chem Soc. 2017 Apr 13;:
Authors: Wang T, Jo H, DeGrado WF, Hong M
Abstract
Water is essential for protein folding and assembly of amyloid fibrils. Internal water cavities have been proposed for several amyloid fibrils, but no direct structural and dynamical data have been reported on the water...
[NMR paper] Formation kinetics and structural features of Beta-amyloid aggregates by sedimented solute NMR.
Formation kinetics and structural features of Beta-amyloid aggregates by sedimented solute NMR.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif Related Articles Formation kinetics and structural features of Beta-amyloid aggregates by sedimented solute NMR.
Chembiochem. 2013 Sep 23;14(14):1891-7
Authors: Bertini I, Gallo G, Korsak M, Luchinat C, Mao J, Ravera E
Abstract
The accumulation of soluble toxic beta-amyloid (A?)...
nmrlearner
Journal club
0
04-24-2014 08:34 PM
Resolution of Oligomeric Species during the Aggregationof A?1–40 Using 19F NMR
Resolution of Oligomeric Species during the Aggregationof A?1–40 Using 19F NMR
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bichaw/0/bichaw.ahead-of-print/bi400027y/aop/images/medium/bi-2013-00027y_0007.gif
Biochemistry
DOI: 10.1021/bi400027y
http://feeds.feedburner.com/~ff/acs/bichaw?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/bichaw/~4/wLipGWfnP6c
More...
nmrlearner
Journal club
0
03-09-2013 11:05 AM
[NMR paper] Resolution of Oligomeric Species during the Aggregation of A?1-40 Using 19F NMR.
Resolution of Oligomeric Species during the Aggregation of A?1-40 Using 19F NMR.
Resolution of Oligomeric Species during the Aggregation of A?1-40 Using 19F NMR.
Biochemistry. 2013 Feb 27;
Authors: Suzuki Y, Brender JR, Soper MT, Krishnamoorthy J, Zhou Y, Ruotolo BT, Kotov NA, Ramamoorthy A, Marsh EN
Abstract
In the commonly used nucleation-dependent model of protein aggregation, aggregation proceeds only after a lag phase in which the concentration of energetically unfavorable nuclei reaches a critical value. The formation of...
nmrlearner
Journal club
0
03-01-2013 09:57 PM
[NMR paper] The cellular prion protein traps Alzheimer's A? in an oligomeric form and disassembles amyloid fibers.
The cellular prion protein traps Alzheimer's A? in an oligomeric form and disassembles amyloid fibers.
Related Articles The cellular prion protein traps Alzheimer's A? in an oligomeric form and disassembles amyloid fibers.
FASEB J. 2013 Jan 30;
Authors: Younan ND, Sarell CJ, Davies P, Brown DR, Viles JH
Abstract
There is now strong evidence to show that the presence of the cellular prion protein (PrP(C)) mediates amyloid-? (A?) neurotoxicity in Alzheimer's disease (AD). Here, we probe the molecular details of the interaction between PrP(C)...
nmrlearner
Journal club
0
02-03-2013 10:19 AM
Structures Behind the Amyloid Aggregation of ?-Synuclein: An NMR Based Approach.
Structures Behind the Amyloid Aggregation of ?-Synuclein: An NMR Based Approach.
Structures Behind the Amyloid Aggregation of ?-Synuclein: An NMR Based Approach.
Curr Protein Pept Sci. 2011 Feb 24;
Authors: Orcellet ML, Fernández CO
The misfolding of proteins into a toxic conformation is proposed to be at the molecular foundation of a number of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Evidence that ?-synuclein amyloidogenesis plays a causative role in the development of Parkinson's disease is furnished by a...