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

Jacek Jasiecki; Monika Targońska; Anna Janaszak-Jasiecka; Leszek Kalinowski; Krzysztof Waleron; Bartosz Wasąg

doi:10.1016/j.cbi.2023.110783

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

Abstract

Alzheimer’s disease (AD) pathogenesis has been attributed to extracellular aggregates of amyloid β (Aβ) plaques and neuroﬁbrillary tangles in the human brain. It has been reported that butyrylcholinesterase (BChE) also accumulates in the brain Aβ 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.

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Authors (6)

Jacek Jasiecki
Monika Targońska
Anna Janaszak-Jasiecka
Leszek Kalinowski prof. dr hab. lek.med.
Krzysztof Waleron
Bartosz Wasąg

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Articles

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artykuły w czasopismach

Published in:

CHEMICO-BIOLOGICAL INTERACTIONS no. 386,
ISSN: 0009-2797

Language:

English

Publication year:

2023

Bibliographic description:

Jasiecki J., Targońska M., Janaszak-Jasiecka A., Kalinowski L., Waleron K., Wasąg B.: Butyrylcholinesterase signal sequence self-aggregates and enhances amyloid fibril formation in vitro// CHEMICO-BIOLOGICAL INTERACTIONS -Vol. 386, (2023), s.110783-

DOI:

10.1016/j.cbi.2023.110783

Sources of funding:

This work was sup-ported by the Polish National Science Center (grant No 2017/01/X/NZ 4/01522) to J.J. and by the Ministry of Education and Science Poland, grant no. 10/E-389/SPUB/SP/2020.

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