Different effects of Alzheimer's peptide Aβ(1–40) oligomers and fibrils on supported lipid membranes

Canale, Claudio; Seghezza, Silvia; Vilasi, Silvia; Carrotta, Rita; Bulone, Donatella; Diaspro, Alberto; Biagio, Pier Luigi San; Dante, Silvia

doi:10.1016/j.bpc.2013.07.010

Cited by 54 publications

(52 citation statements)

References 26 publications

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“…Since proper membrane function requires balanced structural and mechanical properties, our AFM data provide additional perspective on how polyQ aggregates might hamper cellular activity. Our observation of the enhanced bilayer rigidity by polyQ adsorption and insertion is consistent with previous AFM force measurements, which showed that larger puncture forces are required for bilayers exposed to amyloid-β prefibrillar oligomers [21, 54]. Using an AFM mode referred to as the scanning probe acceleration microscopy (SPAM), Legleiter and coworkers measured the maximum tapping force (F max ) and minimal tapping force (F min ) of lipid bilayers during each tapping event [24, 25, 49, 55].…”

Section: Discussionsupporting

confidence: 91%

“…In addition, cytotoxicity was conserved when cytosolic aggregates were administered externally [13, 19]. In line with the membrane permeabilization mechanism, many amyloidogogenic proteins and peptides were found to reorganize membrane structure, such as α-synuclein [20], amyloid-β [21], islet amyloid polypeptide [22], and prion protein fragment [23]. Membrane disruption by polyQ aggregates has also been observed.…”

Section: Introductionmentioning

confidence: 99%

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Polyglutamine aggregates impair lipid membrane integrity and enhance lipid membrane rigidity

Khadka

She

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Lipid membranes are suggested as the primary target of amyloid aggregates. We study aggregates formed by a polyglutamine (polyQ) peptide, and their disruptive effect on lipid membranes. Using solution atomic force microscopy (AFM), we observe polyQ oligomers coexisting with short fibrils, which have a twisted morphology that likely corresponds to two intertwined oligomer strings. Fourier transform infrared spectroscopy reveals that the content of β-sheet enriched aggregates increases with incubation time. Using fluorescence microscopy, we find that exposure to polyQ aggregates results in deflated morphology of giant unilamellar vesicles. PolyQ aggregates induced membrane disruption is further substantiated by time-dependent calcein leakage from the interior to the exterior of lipid vesicles. Detailed structural and mechanical perturbations of lipid membranes are revealed by solution AFM. We find that membrane disruption by polyQ aggregates proceeds by a two-step process, involving partial and full disruption. In addition to height contrast, the resulting partially and fully disrupted bilayers have distinct rigidity and adhesion force properties compared to the intact bilayer. Specifically, the bilayer rigidity increases as the intact bilayer becomes partially and fully disrupted. Surprisingly, the adhesion force first decreases and then increases during the disruption process. By resolving individual fibrils deposited on bilayer surface, we show that both the length and the number of fibrils can increase with incubation time. Our results highlight that membrane disruption could be the molecular basis of polyQ aggregates induced cytotoxicity.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Polyglutamine aggregates impair lipid membrane integrity and enhance lipid membrane rigidity

Khadka

She

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…DLPC SLBs facilitate the rapid formation of globular aggregates on the bilayer surface of, and possibly within, the membrane. In contrast, most reports of membrane-mediated A␤ aggregation using AFM demonstrate the formation of conventional fibrils (41,47,48). This membrane-associated aggregation is probably responsible for the bilayer disruption, despite not occurring through the canonical amyloid formation pathway.…”

Section: Resultsmentioning

confidence: 81%

Reduced Lipid Bilayer Thickness Regulates the Aggregation and Cytotoxicity of Amyloid-β

Korshavn

Satriano

Lin

et al. 2017

Journal of Biological Chemistry

150

158

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Edited by Paul E. FraserThe aggregation of amyloid-␤ (A␤) on lipid bilayers has been implicated as a mechanism by which A␤ exerts its toxicity in Alzheimer's disease (AD). Lipid bilayer thinning has been observed during both oxidative stress and protein aggregation in AD, but whether these pathological modifications of the bilayer correlate with A␤ misfolding is unclear. Here, we studied peptide-lipid interactions in synthetic bilayers of the shortchain lipid dilauroyl phosphatidylcholine (DLPC) as a simplified model for diseased bilayers to determine their impact on A␤ aggregate, protofibril, and fibril formation. A␤ aggregation and fibril formation in membranes composed of dioleoyl phosphatidylcholine (DOPC) or 1-palmitoyl-2-oleoyl phosphatidylcholine mimicking normal bilayers served as controls. Differences in aggregate formation and stability were monitored by a combination of thioflavin-T fluorescence, circular dichroism, atomic force microscopy, transmission electron microscopy, and NMR. Despite the ability of all three lipid bilayers to catalyze aggregation, DLPC accelerates aggregation at much lower concentrations and prevents the fibrillation of A␤ at low micromolar concentrations. DLPC stabilized globular, membrane-associated oligomers, which could disrupt the bilayer integrity. DLPC bilayers also remodeled preformed amyloid fibrils into a pseudo-unfolded, molten globule state, which resembled on-pathway, protofibrillar aggregates. Whereas the stabilized, membrane-associated oligomers were found to be nontoxic, the remodeled species displayed toxicity similar to that of conventionally prepared aggregates. These results provide mechanistic insights into the roles that pathologically thin bilayers may play in A␤ aggregation on neuronal bilayers, and pathological lipid oxidation may contribute to A␤ misfolding.

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“…Studies have shown that Aβ aggregation is one of the underlying causes of AD (Canale et al, 2013). In the present study, Aβ was administered via intracerebral injection to rats to induce AD.…”

Section: Discussionmentioning

confidence: 92%

Effect of phosphatidylserine on memory in patients and rats with Alzheimer’s disease

Zhang¹,

Yang²,

Guo³

2015

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the effect of phosphatidylserine (PS) on memory of patients and rats with Alzheimer's disease (AD). In total, 57 AD patients were recruited from our hospital, and were divided into two groups: 25 in the control group and 32 in the observation group. Next, 300 mg/d of PS was given to the rats in the observation group for 12 continuous weeks based on the control group. AD rats were divided into three groups: control group, PS 30 mg/kg group, and PS 15 mg/kg group. Learning memory ability and free radical levels in the brain were detected after treatment. In AD patients, vocabulary and picture matching scores in the two treatment groups increased after treatment (P < 0.05). Moreover, the scores in the treated group were significantly greater than the control group (P < 0.05). In AD rats, PS treatment reduced the escape latent period of AD rats, increased SOD and OH -, and decreased acetylcholinesterase levels (P < 0.05). Compared with PS 15 mg/kg, PS 30 mg/kg group was significantly more efficacious (P < 0.05). Compared with the AD model group, hippocampal cells showed normal arrangement, karyopyknosis decreased, and the pathological changes in the two PS groups were considerable. In conclusion, PS decreased cholinesterase, improved memory, and improved hippocampal inflammation injury in AD brains by increasing SOD and OH -levels.

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Different effects of Alzheimer's peptide Aβ(1–40) oligomers and fibrils on supported lipid membranes

Cited by 54 publications

References 26 publications

Polyglutamine aggregates impair lipid membrane integrity and enhance lipid membrane rigidity

Polyglutamine aggregates impair lipid membrane integrity and enhance lipid membrane rigidity

Reduced Lipid Bilayer Thickness Regulates the Aggregation and Cytotoxicity of Amyloid-β

Effect of phosphatidylserine on memory in patients and rats with Alzheimer’s disease

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