SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Purification of Full-Length β-Secretase Involved in Alzheimer’s Disease, and Proteomic Identification of Binding Partners

Ly, L; Parsons, R; Austen, B (2020) Purification of Full-Length β-Secretase Involved in Alzheimer’s Disease, and Proteomic Identification of Binding Partners. Journal of Biomedical Science and Engineering, 13 (01). pp. 1-12. ISSN 1937-6871 https://doi.org/10.4236/jbise.2020.131001
SGUL Authors: Austen, Brian Maxwell

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

β-Secretase (BACE1 or β-site APP cleaving enzyme) is an acid protease that releases the neurotoxic 40 - 42 residue peptides (β-amyloid or A-β) from its glycoprotein precursor, (APP or amyloid precursor protein) which when released in brain is thought to give rise to cognitive decline in patients with Alzheimer’s Disease. Most structural studies on β-secretase have previously been performed with recombinant forms of the protease, in which the transmembrane coding region has been deleted. However, interactions with proteins of the same species are best studied using the full-length β-secretase as interactions are likely to be influenced by the hydrophobic nature and localization of its transmembrane regions. Here we develop a multi-step purification procedure that isolates a complex containing BACE1 from recombinant human cells using mild detergents in a procedure that retains other proteins within the complex and remains active in its β-site APP cleaving activity. Some of these proteins, eg reticulon 4, are identified by proteomics, and are known by previous studies performed by others to regulate the activity of BACE1 against APP. These interactions may aid the development of small proteins and peptides that could inhibit the release of aggregated forms of β-amyloid, and thus be useful therapeutically.

Item Type: Article
Additional Information: Copyright © 2020 by author(s) and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Journal of Biomedical Science and Engineering
ISSN: 1937-6871
Dates:
DateEvent
30 January 2020Published
27 January 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
URI: http://openaccess.sgul.ac.uk/id/eprint/111763
Publisher's version: https://doi.org/10.4236/jbise.2020.131001

Actions (login required)

Edit Item Edit Item