Comparison of the amyloid pore forming properties of rat and human Alzheimer’s beta-amyloid peptide 1-42: Calcium imaging data

Scala, Coralie Di; Yahi, Nouara; Flores, Alessandra; Boutemeur, Sonia; Kourdougli, Nazim; Chahinian, Henri; Fantini, Jacques

doi:10.1016/j.dib.2016.01.019

Cited by 8 publications

(4 citation statements)

References 11 publications

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“…To test the therapeutic potential of AmyP53, we developed a sensitive amyloid pore assay based on the detection of Ca 2+ fluxes induced by amyloid pore oligomers generated in the minutes following the addition of nanomolar concentrations of Aβ1-42 or α-syn to recipient SH-SY5Y cells [32,33]. Using this assay, we demonstrated that AmyP53 prevents the formation of such amyloid pores (both wild type Aβ and α-syn, but also mutated forms including A30P, E46K and A53T that are associated with inherited forms of PD) [32].…”

Section: Introductionmentioning

confidence: 99%

Gene Therapy Strategy for Alzheimer’s and Parkinson’s Diseases Aimed at Preventing the Formation of Neurotoxic Oligomers in SH-SY5Y Cells

El‐Battari

Rodriguez

Chahinian

et al. 2021

IJMS

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We present here a gene therapy approach aimed at preventing the formation of Ca2+-permeable amyloid pore oligomers that are considered as the most neurotoxic structures in both Alzheimer’s and Parkinson’s diseases. Our study is based on the design of a small peptide inhibitor (AmyP53) that combines the ganglioside recognition properties of the β-amyloid peptide (Aβ, Alzheimer) and α-synuclein (α-syn, Parkinson). As gangliosides mediate the initial binding step of these amyloid proteins to lipid rafts of the brain cell membranes, AmyP53 blocks, at the earliest step, the Ca2+ cascade that leads to neurodegeneration. Using a lentivirus vector, we genetically modified brain cells to express the therapeutic coding sequence of AmyP53 in a secreted form, rendering these cells totally resistant to oligomer formation by either Aβ or α-syn. This protection was specific, as control mCherry-transfected cells remained fully sensitive to these oligomers. AmyP53 was secreted at therapeutic concentrations in the supernatant of cultured cells, so that the therapy was effective for both transfected cells and their neighbors. This study is the first to demonstrate that a unique gene therapy approach aimed at preventing the formation of neurotoxic oligomers by targeting brain gangliosides may be considered for the treatment of two major neurodegenerative disorders, Alzheimer’s and Parkinson’s diseases.

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Section: Introductionmentioning

confidence: 99%

Gene Therapy Strategy for Alzheimer’s and Parkinson’s Diseases Aimed at Preventing the Formation of Neurotoxic Oligomers in SH-SY5Y Cells

El‐Battari

Rodriguez

Chahinian

et al. 2021

IJMS

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“…The molecular mechanisms of Aβ neurotoxicity is complex and not fully understood. Aβ can damage neurons through dysregulation of cellular ionic homeostasis by two main routes: (i) modulation of certain ion channels in plasma or intracellular membranes 18 , 19 or (ii) permeabilization of cell membranes through direct membrane insertion and ion channel formation 7 , 20 – 33 . Aβ 1-42 and Aβ 1-40 induced ion conductance in lipid membranes 20 , 27 , 34 .…”

Section: Introductionmentioning

confidence: 99%

“…of cellular ionic homeostasis by two main routes: (i) modulation of certain ion channels in plasma or intracellular membranes 18,19 or (ii) permeabilization of cell membranes through direct membrane insertion and ion channel formation 7,[20][21][22][23][24][25][26][27][28][29][30][31][32][33] . Aβ 1-42 and Aβ 1-40 induced ion conductance in lipid membranes 20,27,34 .…”

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confidence: 99%

The structure of tyrosine-10 favors ionic conductance of Alzheimer’s disease-associated full-length amyloid-β channels

Karkisaval,

Hassan,

Nguyen

et al. 2024

Nat Commun

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Amyloid β (Aβ) ion channels destabilize cellular ionic homeostasis, which contributes to neurotoxicity in Alzheimer’s disease. The relative roles of various Aβ isoforms are poorly understood. We use bilayer electrophysiology, AFM imaging, circular dichroism, FTIR and fluorescence spectroscopy to characterize channel activities of four most prevalent Aβ peptides, Aβ1-42, Aβ1-40, and their pyroglutamylated forms (AβpE3-42, AβpE3-40) and correlate them with the peptides’ structural features. Solvent-induced fluorescence splitting of tyrosine-10 is discovered and used to assess the sequestration from the solvent and membrane insertion. Aβ1-42 effectively embeds in lipid membranes, contains large fraction of β-sheet in a β-barrel-like structure, forms multi-subunit pores in membranes, and displays well-defined ion channel features. In contrast, the other peptides are partially solvent-exposed, contain minimal β-sheet structure, form less-ordered assemblies, and produce irregular ionic currents. These findings illuminate the structural basis of Aβ neurotoxicity through membrane permeabilization and may help develop therapies that target Aβ-membrane interactions.

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“…The mechanism of toxicity involves the penetration of small oligomers into the membrane and formation of unregulated ion channels, which lead to ion leakage and, ultimately, cell death [11][12][13][14][15]. Scala et al found that calcium could pretreat through the pore formed by beta-amyloid peptide [16]. However, the hypothesis of an ionic channel formed from Aβ peptides is still under the debated.…”

Section: Introductionmentioning

confidence: 99%

Pore Formation Mechanism of A-Beta Peptide on the Fluid Membrane: A Combined Coarse-Grained and All-Atomic Model

2022

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In Alzheimer’s disease, ion permeability through the ionic channel formed by Aβ peptides on cellular membranes appears to underlie neuronal cell death. An understanding of the formation mechanism of the toxic ionic channel by Aβ peptides is very important, but remains unclear. Our simulation results demonstrated the dynamics and mechanism of channel formation by Aβ1-28 peptides on the DPPC and POPC membrane by the coarse-grained method. The ionic channel formation is driven by the gyration of the radius and solvent accessible molecular surface area of Aβ1-28 peptides. The ionic channel formation mechanism was explored by the free energy profile based on the distribution of the gyration of the radius and solvent accessible molecular surface area of Aβ1-28 peptides on the fluid membrane. The stability and water permeability of the ionic channel formed by Aβ peptides was investigated by all-atomic model simulation. Our simulation showed that the ionic channel formed by Aβ1-28 peptides is very stable and has a good water permeability. This could help us to understand the pore formation mechanism by Aβ1-28 peptides on the fluidic membrane. It also provides us with a guideline by which to understand the toxicity of Aβ1-28 peptides’ pores to the cell.

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Comparison of the amyloid pore forming properties of rat and human Alzheimer’s beta-amyloid peptide 1-42: Calcium imaging data

Cited by 8 publications

References 11 publications

Gene Therapy Strategy for Alzheimer’s and Parkinson’s Diseases Aimed at Preventing the Formation of Neurotoxic Oligomers in SH-SY5Y Cells

Gene Therapy Strategy for Alzheimer’s and Parkinson’s Diseases Aimed at Preventing the Formation of Neurotoxic Oligomers in SH-SY5Y Cells

The structure of tyrosine-10 favors ionic conductance of Alzheimer’s disease-associated full-length amyloid-β channels

Pore Formation Mechanism of A-Beta Peptide on the Fluid Membrane: A Combined Coarse-Grained and All-Atomic Model

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