Single Point Mutation from E22-to-K in Aβ Initiates Early-Onset Alzheimer’s Disease by Binding with Catalase
Joint Authors
Yue, Xiangpei
He, Rongqiao
Jiang, Wenjing
Zhao, Shengjie
YanYu, Wenjing
Yao, Dandan
Fei, Xuechao
Ai, Li
Di, Yalan
Zhang, Jingnan
Lyu, Jihui
Tong, Zhiqian
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-21, 21 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-12-24
Country of Publication
Egypt
No. of Pages
21
Main Subjects
Abstract EN
Amyloid-beta (Aβ) is a critical etiological factor for late-onset familial Alzheimer’s disease (AD).
However, an early-onset AD has been found to be related with an Aβ mutation in glutamic acid 22-to-lysine (Italian type E22K).
Why only one single point mutation at E22 residue induces AD remains unclear.
Here, we report that a Chinese familial AD pedigree with E22K mutation was associated with higher levels of serum hydrogen peroxide (H2O2) and lower activity of catalase (a H2O2 degrading enzyme) than controls.
Further, we found that E22K binding with catalase caused more severe H2O2 accumulation in the brains of E22K-injected rats than Aβ-injected rats.
Unexpectedly, H2O2 bound with the mutation site 22K residue of E22K and elicited more rapid aggregation of E22K than Aβ in vitro.
Moreover, H2O2 acted with E22K synergistically to induce higher cellular toxicity than with Aβ.
Notably, intrahippocampal infusion of E22K led to more severe plaque deposition, neuron death, and more rapid memory decline than Aβ-injected rats.
However, L-cysteine, a H2O2 scavenger, not only prevented self-aggregation of E22K but also reduced H2O2-promoted E22K assembly in vitro; subsequently, it alleviated Alzheimer-related phenotypes.
Hence, E22K binding with catalase promotes the early onset of familial AD, and L-cys may reverse this disease.
American Psychological Association (APA)
Jiang, Wenjing& YanYu, Wenjing& Yao, Dandan& Fei, Xuechao& Ai, Li& Di, Yalan…[et al.]. 2020. Single Point Mutation from E22-to-K in Aβ Initiates Early-Onset Alzheimer’s Disease by Binding with Catalase. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-21.
https://search.emarefa.net/detail/BIM-1204685
Modern Language Association (MLA)
Jiang, Wenjing…[et al.]. Single Point Mutation from E22-to-K in Aβ Initiates Early-Onset Alzheimer’s Disease by Binding with Catalase. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-21.
https://search.emarefa.net/detail/BIM-1204685
American Medical Association (AMA)
Jiang, Wenjing& YanYu, Wenjing& Yao, Dandan& Fei, Xuechao& Ai, Li& Di, Yalan…[et al.]. Single Point Mutation from E22-to-K in Aβ Initiates Early-Onset Alzheimer’s Disease by Binding with Catalase. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-21.
https://search.emarefa.net/detail/BIM-1204685
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204685