Role of the cell membrane interface in modulating production and uptake of Alzheimer's beta amyloid protein

Prashant Bharadwaj; Tanya Solomon; Chris J Malajczuk; Ricardo L Mancera; Mark Howard; Damien W M Arrigan; Philip Newsholme; Ralph N Martins

doi:10.1016/j.bbamem.2018.03.015

Role of the cell membrane interface in modulating production and uptake of Alzheimer's beta amyloid protein

Biochim Biophys Acta Biomembr. 2018 Sep;1860(9):1639-1651. doi: 10.1016/j.bbamem.2018.03.015. Epub 2018 Mar 21.

Authors

Prashant Bharadwaj¹, Tanya Solomon², Chris J Malajczuk², Ricardo L Mancera², Mark Howard³, Damien W M Arrigan⁴, Philip Newsholme², Ralph N Martins⁵

Affiliations

¹ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Australia; School of Pharmacy and Biomedical Sciences and Curtin Health Innovation Research Institute, Curtin University, GPO Box U1987, Perth, Western Australia 6845, Australia. Electronic address: p.bharadwaj@ecu.edu.au.
² School of Pharmacy and Biomedical Sciences and Curtin Health Innovation Research Institute, Curtin University, GPO Box U1987, Perth, Western Australia 6845, Australia.
³ Centre for Microscopy, Characterisation and Analysis (CMCA), The University of Western, Australia.
⁴ School of Molecular and Life Sciences, Curtin Institute for Functional Molecules and Interfaces, Curtin University, GPO Box U1987, Perth, Western Australia 6845, Australia.
⁵ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Australia; School of Biomedical Science, Macquarie University, Australia; School of Psychiatry and Clinical Neurosciences, University of Western Australia, Australia.

PMID: 29572033
DOI: 10.1016/j.bbamem.2018.03.015

Abstract

The beta amyloid protein (Aβ) plays a central role in Alzheimer's disease (AD) pathogenesis and its interaction with cell membranes in known to promote mutually disruptive structural perturbations that contribute to amyloid deposition and neurodegeneration in the brain. In addition to protein aggregation at the membrane interface and disruption of membrane integrity, growing reports demonstrate an important role for the membrane in modulating Aβ production and uptake into cells. The aim of this review is to highlight and summarize recent literature that have contributed insight into the implications of altered membrane composition on amyloid precursor protein (APP) proteolysis, production of Aβ, its internalization in to cells via permeabilization and receptor mediated uptake. Here, we also review the various membrane model systems and experimental tools used for probing Aβ-membrane interactions to investigate the key mechanistic aspects underlying the accumulation and toxicity of Aβ in AD.

Keywords: APP proteolysis; Membrane fluidity; Membrane permeabilization; Receptor mediated uptake of beta amyloid.

Publication types

Review