Butyrylcholinesterase signal sequence self-aggregates and enhances amyloid fibril formation in vitro

被引：2

作者：

Jasiecki, Jacek ^{[1
]}

Targonska, Monika

Janaszak-Jasiecka, Anna ^{[3
]}

Kalinowski, Leszek ^{[3
,4
]}

Waleron, Krzysztof ^{[1
]}

Wasag, Bartosz ^{[2
,5
]}

机构：

[1] Med Univ Gdansk, Fac Pharm, Dept Pharmaceut Microbiol, PL-80416 Gdansk, Poland

[2] Med Univ Gdansk, Dept Biol & Med Genet, PL-80210 Gdansk, Poland

[3] Med Univ Gdansk, Dept Med Lab Diagnost, Fahrenheit Biobank BBMRI Pl, PL-80211 Gdansk, Poland

[4] Gdansk Univ Technol, BioTechMed Ctr, Dept Mech Mat & Struct, PL-80233 Gdansk, Poland

[5] Univ Clin Ctr, Lab Clin Genet, PL-80952 Gdansk, Poland

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2023年 / 386卷

关键词：

Alzheimer's disease; Butyrylcholinesterase; Pseudocholinesterase; Amyloid; Aggregation; Cross-seeding; (1-42)-INDUCED OXIDATIVE STRESS; ALZHEIMERS-DISEASE; A-BETA; PROTEIN; PEPTIDE; PLAQUES; PATHOGENESIS; CHEMISTRY; TOXICITY; NEURONS;

D O I：

10.1016/j.cbi.2023.110783

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：

Alzheimer's disease (AD) pathogenesis has been attributed to extracellular aggregates of amyloid beta (A beta) plaques and neurofibrillary tangles in the human brain. It has been reported that butyrylcholinesterase (BChE) also accumulates in the brain A beta plaques in AD. We have previously found that the BChE substitution in 5 ' UTR caused an in-frame N-terminal extension of 41 amino acids of the BChE signal peptide. The resultant variant with a 69 amino acid signal peptide, designated N-BChE, could play a role in AD development. Here, we report that the signal sequence of the BChE, if produced in an extended 69 aa version, can self-aggregate and could form seeds that enhance amyloid fibril formation in vitro in a dose-dependent manner and create larger co-aggregates. Similar phenomena could have been observed in the human brain if such an extended form of the signal sequence had been, in some circumstances, translated.

引用

页数：9

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