Why Aβ42 Is Much More Toxic than Aβ40

被引：30
作者：
Phillipse, James C. [1 ]
机构：
[1] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA
来源：
ACS CHEMICAL NEUROSCIENCE | 2019年 / 10卷 / 06期
关键词：
Protein; function; amino acid; sequence; evolutionary; criticality; self-organized; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; TRANSMEMBRANE DOMAIN; DIMERIZATION; OLIGOMERIZATION; MUTATIONS; RESIDUES; GAMMA;
D O I：
10.1021/acschemneuro.9b00068
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Amyloid precursor A4 (770 amino acids (aa)) dimerizes and aggregates, as do its C-terminal (99 aa) and amyloid A beta (40,42 aa A beta 40,A beta 42) fragments. The titled question has been discussed extensively, and here it is addressed further using thermodynamic scaling theory to analyze mutational trends in structural factors and kinetics. Special attention is given to Family Alzheimer's disease mutations in C99 outside A beta 42 centered on A beta 46. The scaling analysis is connected to extensive C99 docking simulations which included membranes (Sun et al. J. Chem. Inf. Model. 2017, 57, 1375-1387), thereby confirming their C99 results and extending them to A4.
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收藏
页码：2843 / 2847
页数：9
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