Systematic Search for a Predictor for the Clinical Observables of Alzheimer's Disease

被引:3
|
作者
Das, Atanu [1 ,2 ]
机构
[1] CSIR Natl Chem Lab, Phys & Mat Chem Div, Pune 411008, Maharashtra, India
[2] Acad Sci & Innovat Res AcSIR, Ghaziabad 201002, India
来源
JOURNAL OF PHYSICAL CHEMISTRY B | 2021年 / 125卷 / 44期
关键词
AMYLOID-BETA-PROTEIN; ATOMIC-RESOLUTION STRUCTURE; THIOFLAVIN T FLUORESCENCE; PRECURSOR PROTEIN; AGGREGATION; DYNAMICS; A-BETA(42); MUTATION; FIBRILS; IMPLEMENTATION;
D O I
10.1021/acs.jpcb.1c06725
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
One of the prevailing life-threatening incurable neurodegenerative diseases that are presently endangering human society as a whole, and hence, baffling the entire spectrum of the scientific and pharmaceutical world, is Alzheimer's disease (AD). AD is a manifestation of self-assembly of both wild-type (sporadic) and mutated (familial) forms of the amyloid-beta peptide, a proteolytic product of the amyloid precursor protein, where the self-assembly results in the genesis of pathogenic fibrillar aggregates. Currently prevailing diagnostic and hence therapeutic challenges originate from the unavailability of a specific predictor for clinical observables. The continuous emergence of novel pathogenic mutants with unpredictable phenotypes adds immensely to the nonspecific nature of the problem. The current research reports a simple physical parameter, the binding affinity of a protofilament to its protofibril, which predicts the clinical observables of familial AD with astounding accuracy and more importantly, without any adjustable parameters.
引用
收藏
页码:12177 / 12186
页数:10
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