Changes in lipid membranes may trigger amyloid toxicity in Alzheimer's disease

被引：77

作者：

Drolle, Elizabeth ^{[1
,2
]}

Negoda, Alexander ^{[3
]}

Hammond, Keely ^{[4
]}

Pavlov, Evgeny ^{[3
,5
]}

Leonenko, Zoya ^{[1
,2
,4
]}

机构：

[1] Univ Waterloo, Dept Biol, Waterloo, ON, Canada

[2] Univ Waterloo, Waterloo Inst Nanotechnol, Waterloo, ON, Canada

[3] Dalhousie Univ, Dept Physiol & Biophys, Halifax, NS, Canada

[4] Univ Waterloo, Dept Phys & Astron, Waterloo, ON, Canada

[5] NYU, Coll Dent, Dept Basic Sci, New York, NY USA

来源：

PLOS ONE | 2017年 / 12卷 / 08期

基金：

加拿大自然科学与工程研究理事会;

关键词：

ATOMIC-FORCE MICROSCOPY; BETA-PROTEIN; PEPTIDE; GANGLIOSIDE; CHOLESTEROL; AGGREGATION; MECHANISMS; FIBRILS; DOMAINS; FIBRILLOGENESIS;

D O I：

10.1371/journal.pone.0182194

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Amyloid-beta peptides (A beta), implicated in Alzheimer's disease (AD), interact with the cellular membrane and induce amyloid toxicity. The composition of cellular membranes changes in aging and AD. We designed multi-component lipid models to mimic healthy and diseased states of the neuronal membrane. Using atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM) and black lipid membrane (BLM) techniques, we demonstrated that these model membranes differ in their nanoscale structure and physical properties, and interact differently with A beta(1-42). Based on our data, we propose a new hypothesis that changes in lipid membrane due to aging and AD may trigger amyloid toxicity through electrostatic mechanisms, similar to the accepted mechanism of antimicrobial peptide action. Understanding the role of the membrane changes as a key activating amyloid toxicity may aid in the development of a new avenue for the prevention and treatment of AD.

引用

页数：16

共 58 条

[1] Membrane cholesterol content plays a key role in the neurotoxicity of β-amyloid: implications for Alzheimer's disease
Abramov, Andrey Y.
Ionov, Maksim
Pavlov, Evgeny
Duchen, Michael R.
[J]. AGING CELL, 2011, 10 (04) : 595 - 603
[2] An YH, 1998, J BIOMED MATER RES, V43, P338, DOI 10.1002/(SICI)1097-4636(199823)43:3<338::AID-JBM16>3.0.CO
[3] 2-B
[4] Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease - a review
Ariga, Toshio
McDonald, Michael P.
Yu, Robert K.
[J]. JOURNAL OF LIPID RESEARCH, 2008, 49 (06) : 1157 - 1175
[5] SURFACE-POTENTIALS AND ELECTRIC-DIPOLE MOMENTS OF GANGLIOSIDE AND PHOSPHOLIPID MONOLAYERS - CONTRIBUTION OF THE POLAR HEADGROUP AT THE WATER LIPID INTERFACE
BEITINGER, H
VOGEL, V
MOBIUS, D
RAHMANN, H
[J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1989, 984 (03) : 293 - 300
[6] Using neurolipidomics to identify phospholipid mediators of synaptic (dys)function in Alzheimer's Disease
Bennett, Steffany A. L.
Valenzuela, Nicolas
Xu, Hongbin
Franko, Bettina
Fai, Stephen
Figeys, Daniel
[J]. FRONTIERS IN PHYSIOLOGY, 2013, 4
[7] DIPOLE POTENTIAL OF LIPID-MEMBRANES
BROCKMAN, H
[J]. CHEMISTRY AND PHYSICS OF LIPIDS, 1994, 73 (1-2) : 57 - 79
[8] Biophysical insights into how surfaces, including lipid membranes, modulate protein aggregation related to neurodegeneration
Burke, Kathleen A.
Yates, Elizabeth A.
Legleiter, Justin
[J]. FRONTIERS IN NEUROLOGY, 2013, 4
[9] CALDERON RO, 1995, J NEUROCHEM, V64, P424
[10] Ganglioside GM1-mediated amyloid-beta fibrillogenesis and membrane disruption
Chi, Eva Y.
Frey, Shelli L.
Lee, Ka Yee C.
[J]. BIOCHEMISTRY, 2007, 46 (07) : 1913 - 1924

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