Interactions of A?(1?40) with Glycerophosphocholine and Intact Erythrocyte Membranes: Fluorescence and Circular Dichroism Studies

Mandal, Pravat K.; McClure, Richard J.; Pettegrew, Jay W.

doi:10.1007/s11064-004-7036-0

Cited by 8 publications

(1 citation statement)

References 24 publications

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“…This was observed using intact erythrocyte membranes. Glycerophosphocholine, a breakdown product of phospholipids, itself increased in AD individuals, was shown to enhance the aggregation of Ab in the erythrocyte membranes (Mandal et al, 2004). That lipid rafts may be important sites for not only cleavage of APP into Ab and Ab interactions with membrane lipids, Kawarabayashi et al (2004) reported the possible role of rafts in the formation of neurofibrillary tangles (NFTs).…”

Section: Lipid Modulation Of Amyloid Beta Aggregation and Neurotoxicitymentioning

confidence: 99%

Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

Vestergaard

Hamada

Takagi

2008

Biotech & Bioengineering

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One of the major tasks in understanding the etiopathogenesis of amyloid beta-induced neurotoxicity of Alzheimer's disease (AD), is in fully capturing the large number of the biochemical processes that influence each other during the course of the disease, in vivo. Model membranes possess, as their main strength, the ability to enable the researcher to manipulate a 'biological' microvesicle under a controlled environment. This review narrowly focuses on discussing the exploitation of model membranes for improved understanding of some of the mechanisms governing AD's amyloid beta-induced neurotoxicity. Amyloid beta (Ab) is cleaved from a membranelocated amyloid precursor protein by membrane-located enzymes. The relative spatial localization of the involved biomolecules within the membrane bilayer is crucial in influencing Ab production, its aggregation on the membrane surface or insertion into the membrane, and fibril formation: all important processes in causing neurotoxicity. The lipid composition of the bilayer is similarly important. The review also attempts to highlight current and future challenges in using model membranes for studying biochemical processes.

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Section: Lipid Modulation Of Amyloid Beta Aggregation and Neurotoxicitymentioning

confidence: 99%

Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

Vestergaard

Hamada

Takagi

2008

Biotech & Bioengineering

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Aβ peptide interactions with isoflurane, propofol, thiopental and combined thiopental with halothane: A NMR study

Mandal

Pettegrew

2008

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Abeta peptide is the major component of senile plaques (SP) which accumulates in AD (Alzheimer's disease) brain. Reports from different laboratories indicate that anesthetics interact with Abeta peptide and induce Abeta oligomerization. The molecular mechanism of Abeta peptide interactions with these anesthetics was not determined. We report molecular details for the interactions of uniformly (15)N labeled Abeta40 with different anesthetics using 2D nuclear magnetic resonance (NMR) experiments. At high concentrations both isoflurane and propofol perturb critical amino acid residues (G29, A30 and I31) of Abeta peptide located in the hinge region leading to Abeta oligomerization. In contrast, these three specific residues do not interact with thiopental and subsequently no Abeta oligomerization was observed. However, studies with combined anesthetics (thiopental and halothane), showed perturbation of these residues (G29, A30 and I31) and subsequently Abeta oligomerization was found. Perturbation of these specific Abeta residues (G29, A30 and I31) by different anesthetics could play an important role to induce Abeta oligomerization.

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Cause and consequence of Aβ – Lipid interactions in Alzheimer disease pathogenesis

Rangachari

Dean

Rana

et al. 2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Self-templating propagation of protein aggregate conformations is increasingly becoming a significant factor in many neurological diseases. In Alzheimer disease (AD), intrinsically disordered amyloid-β (Aβ) peptides undergo aggregation that is sensitive to environmental conditions. High-molecular weight aggregates of Aβ that form insoluble fibrils are deposited as senile plaques in AD brains. However, low-molecular weight aggregates called soluble oligomers are known to be the primary toxic agents responsible for neuronal dysfunction. The aggregation process is highly stochastic involving both homotypic (Aβ-Aβ) and heterotypic (Aβ with interacting partners) interactions. Two of the important members of interacting partners are membrane lipids and surfactants, to which Aβ shows a perpetual association. Aβ-membrane interactions have been widely investigated for more than two decades, and this research has provided a wealth of information. Although this has greatly enriched our understanding, the objective of this review is to consolidate the information from the literature that collectively showcases the unique phenomenon of lipid-mediated Aβ oligomer generation, which has largely remained inconspicuous. This is especially important because Aβ aggregate "strains" are increasingly becoming relevant in light of the correlations between the structure of aggregates and AD phenotypes. Here, we will focus on aspects of Aβ-lipid interactions specifically from the context of how lipid modulation generates a wide variety of biophysically and biochemically distinct oligomer sub-types. This, we believe, will refocus our thinking on the influence of lipids and open new approaches in delineating the mechanisms of AD pathogenesis. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy.

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Interactions of A?(1?40) with Glycerophosphocholine and Intact Erythrocyte Membranes: Fluorescence and Circular Dichroism Studies

Cited by 8 publications

References 24 publications

Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

Aβ peptide interactions with isoflurane, propofol, thiopental and combined thiopental with halothane: A NMR study

Cause and consequence of Aβ – Lipid interactions in Alzheimer disease pathogenesis

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