β-amyloid peptide decreases membrane fluidity

Müller, Wernér E.G.; Koch, Sabrina; Eckert, Anne; Hartmann, H.; Scheuer, K.

doi:10.1016/0006-8993(94)01463-r

Cited by 127 publications

(127 citation statements)

References 13 publications

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“…Effects of soluble A␤ 1-40 on SPM fluidity are consistent with findings reported earlier (14). Another study, however, found that A␤ 1-40 reduced fluidity of a brain homogenate preparation (13). In both our previous study and the current study, we used isolated SPM.…”

Section: Discussionsupporting

confidence: 91%

“…In addition, fluidity in SPM was determined using the pyrene probe, whereas polarization of the fluorescent probe diphenylhexatriene was used in the brain homogenate preparation. A␤ appears to behave differently in a membrane preparation, as compared with a heterogenous brain homogenate system (13).…”

Section: Discussionmentioning

confidence: 97%

“…A recent study from Cotman and co-workers (12) showed that A␤ neurotoxicity is independent of stereoisomerspecific ligand-receptor interaction because both all-D-and all-L-stereoisomers of A␤ [25][26][27][28][29][30][31][32][33][34][35] and A␤ had similar neurotoxic activity. This finding suggests that A␤ modulates membrane function by a nonreceptor-mediated mechanism, potentially as a result of altering the physico-chemical properties of membrane constituents, including lipids and proteins (13)(14)(15)(16). Indeed, previous membrane equilibrium binding experiments have demonstrated that the A␤ [25][26][27][28][29][30][31][32][33][34][35] fragment is highly lipophilic (K P Ͼ 10 2 ); the peptide intercalates deep into the membrane bilayer hydrocarbon core, as determined by small angle x-ray diffraction approaches (15).…”

mentioning

confidence: 99%

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Distribution and Fluidizing Action of Soluble and Aggregated Amyloid β-Peptide in Rat Synaptic Plasma Membranes

Mason

Jacob

Walter

et al. 1999

Journal of Biological Chemistry

127

110

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The effects of soluble and aggregated amyloid ␤-peptide (A␤) on cortical synaptic plasma membrane (SPM) structure were examined using small angle x-ray diffraction and fluorescence spectroscopy approaches. Electron density profiles generated from the x-ray diffraction data demonstrated that soluble and aggregated A␤ 1-40 peptides associated with distinct regions of the SPM. The width of the SPM samples, including surface hydration, was 84 Å at 10°C. Following addition of soluble A␤ 1-40 , there was a broad increase in electron density in the SPM hydrocarbon core ؎0 -15 Å from the membrane center, and a reduction in hydrocarbon core width by 6 Å. By contrast, aggregated A␤ 1-40 contributed electron density to the phospholipid headgroup/hydrated surface of the SPM ؎24 -37 Å from the membrane center, concomitant with an increase in molecular volume in the hydrocarbon core. The SPM interactions observed for A␤ 1-40 were reproduced in a brain lipid membrane system. In contrast to A␤ 1-40 , aggregated A␤ 1-42 intercalated into the lipid bilayer hydrocarbon core ؎0 -12 Å from the membrane center. Fluorescence experiments showed that both soluble and aggregated A␤ 1-40 significantly increased SPM bulk and protein annular fluidity. Physico-chemical interactions of A␤ with the neuronal membrane may contribute to mechanisms of neurotoxicity, independent of specific receptor binding. Alzheimer's disease (AD)1 is a progressive neurodegenerative disorder characterized by the accumulation of neuritic plaques composed of amyloid ␤-peptide (A␤) variants, extracellular matrix components, and apolipoproteins (1, 2). A␤ is an amphipathic, 39 -42-residue peptide that is derived by proteolytic cleavage of the transmembrane glycoprotein, the amyloid precursor protein; the A␤ domain is composed of 28 extracellular and 12-14 transmembrane amino acid residues of amyloid precursor protein (3). An increase in the production and abnormal accumulation of A␤ in the brain has been implicated in the etiology of AD. Several studies have shown that A␤ analogs can directly disrupt neuronal function, contributing to cell death associated with the development of AD (4 -8).It has been postulated that the biological activity of A␤ is related to its ability to form insoluble aggregates in solution (9 -11), although the cellular mechanism of action is not well understood. A recent study from Cotman and co-workers (12) showed that A␤ neurotoxicity is independent of stereoisomerspecific ligand-receptor interaction because both all-D-and all-L-stereoisomers of A␤ [25][26][27][28][29][30][31][32][33][34][35] and A␤ 1-40 had similar neurotoxic activity. This finding suggests that A␤ modulates membrane function by a nonreceptor-mediated mechanism, potentially as a result of altering the physico-chemical properties of membrane constituents, including lipids and proteins (13-16). Indeed, previous membrane equilibrium binding experiments have demonstrated that the A␤ 25-35 fragment is highly lipophilic (K P Ͼ 10 2 ); the peptide intercalates deep into the membra...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

See 1 more Smart Citation

Distribution and Fluidizing Action of Soluble and Aggregated Amyloid β-Peptide in Rat Synaptic Plasma Membranes

Mason

Jacob

Walter

et al. 1999

Journal of Biological Chemistry

127

110

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“…Spectra with an array of delay times were recorded, and the normalized peak areas were plotted versus the delay period. The 13 C, 31 P REDOR pulse sequence contains a 50-kHz 1 H /2 excitation pulse, a cross-polarization period (ϳ45-kHz 1 H field and 40-to 65-kHz 13 C field with a linear ramp over 1.5 ms), a series of rotor-synchronized pulses with XY-8 phase cycling, and an acquisition period with a 100-kHz 1 H decoupling field. The 13 C transmitter was set to 165 ppm, which was close to the carbonyl carbon region of the spectrum.…”

Section: Methodsmentioning

confidence: 99%

“…For each REDOR dephasing period, a pair of S 0 and S 1 spectra was collected without and with the 31 P pulses, respectively. The REDOR dephasing curve was obtained by plotting the normalized 13 C signal attenuation (i.e. (S 0 -S 1 )/S 0 ) as a function of dephasing time.…”

Section: Methodsmentioning

confidence: 99%

Distinct Membrane Disruption Pathways Are Induced by 40-Residue β-Amyloid Peptides

Delgado

Doherty

Cheng

et al. 2016

Journal of Biological Chemistry

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Cellular membrane disruption induced by ␤-amyloid (A␤) peptides has been considered one of the major pathological mechanisms for Alzheimer disease. Mechanistic studies of the membrane disruption process at a high-resolution level, on the other hand, are hindered by the co-existence of multiple possible pathways, even in simplified model systems such as the phospholipid liposome. Therefore, separation of these pathways is crucial to achieve an in-depth understanding of the A␤-induced membrane disruption process. This study, which utilized a combination of multiple biophysical techniques, shows that the peptide-to-lipid (P:L) molar ratio is an important factor that regulates the selection of dominant membrane disruption pathways in the presence of 40-residue A␤ peptides in liposomes. Three distinct pathways (fibrillation with membrane content leakage, vesicle fusion, and lipid uptake through a temporarily stable ionic channel) become dominant in model liposome systems under specific conditions. These individual systems are characterized by both the initial states of A␤ peptides and the P:L molar ratio. Our results demonstrated the possibility to generate simplified A␤-membrane model systems with a homogeneous membrane disruption pathway, which will benefit high-resolution mechanistic studies in the future. Fundamentally, the possibility of pathway selection controlled by P:L suggests that the driving forces for A␤ aggregation and A␤-membrane interactions may be similar at the molecular level.

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Metalloproteins and Metallopeptides – Natural Metallofoldamers

Lykourinou

Ming

2013

Metallofoldamers

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β-amyloid peptide decreases membrane fluidity

Cited by 127 publications

References 13 publications

Distribution and Fluidizing Action of Soluble and Aggregated Amyloid β-Peptide in Rat Synaptic Plasma Membranes

Distribution and Fluidizing Action of Soluble and Aggregated Amyloid β-Peptide in Rat Synaptic Plasma Membranes

Distinct Membrane Disruption Pathways Are Induced by 40-Residue β-Amyloid Peptides

Metalloproteins and Metallopeptides – Natural Metallofoldamers

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