Rat's trick to escape Alzheimer's disease.
Amyloid beta (Abeta) peptides fibril formation and deposition is considered to be the principal pathological hallmark of Alzheimer's disease (AD). However, it remains obscure why AD is precluded by rat/mouse despite the high sequence identity (97%) of rat/mouse Abeta to its human homologue. Based on the recently proposed redox chemistry-based pathogenic model of neurodegenerative diseases, we hypothesize that the lack of key residues of rat/mouse Abeta compared with the human counterpart may account for why rat/mouse is free of AD. At the same time, we propose a new possible redox chemistry-based pathogenic model of AD based on the experimental observations of certain residues in triggering Abeta aggregation. Moreover, it is also interesting to note that non-mammalian Xenopus Abeta contains all the redox chemistry-related key residues and whether it implies that Xenopus Abeta possesses high amyloidogenic potency remains to be determined by further experimental study.
Shen
Lian
L
Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Center for Advanced Study, Shandong University of Technology, Zibo 255049, P. R. China.
Ji
Hong-Fang
HF
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D017124:Conserved Sequence; D003300:Copper / Q000737:chemistry; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D051381:Rats; D016415:Sequence Alignment; D013045:Species Specificity; D014981:Xenopus; D015032:Zinc / Q000737:chemistry
D016229:Amyloid beta-Peptides; D003300:Copper; D015032:Zinc