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288 results on '"Murphy, Regina M."'

10. Necroptosis is associated with Rab27‐independent expulsion of extracellular vesicles containing RIPK3 and MLKL

Author

Gupta, Kartik, primary, Brown, Kyle A., additional, Hsieh, Marvin L., additional, Hoover, Brandon M., additional, Wang, Jianxin, additional, Khoury, Mitri K., additional, Pilli, Vijaya Satish Sekhar, additional, Beyer, Reagan S. H., additional, Voruganti, Nihal R., additional, Chaudhary, Sahil, additional, Roberts, David S., additional, Murphy, Regina M., additional, Hong, Seungpyo, additional, Ge, Ying, additional, and Liu, Bo, additional

Published
2022
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16. Design of peptidyl compounds that affect beta-amyloid aggregation: Importance of surface tension and context

Author

Gibson, Todd J. and Murphy, Regina M.

Subjects
Chemical reaction, Rate of -- Research, Peptides -- Research, Amyloid beta-protein -- Research, Biological sciences, Chemistry
Abstract

Different consequences for beta-amyloid (Abeta) aggregation when arginine is presented as a domain to KLVFF are demonstrated. The peptidyl compound's ability to increase solvent surface tension is the strongest predictor of arginine on Abeta aggregation kinetics.

Published
2005

18. Affinity-based inhibition of beta-amyloid toxicity

Author

Cairo, Christopher W., Strzelec, Andrea, Murphy, Regina M., and Kiessling, Laura L.

Subjects
Amyloid beta-protein -- Physiological aspects, Toxicity testing -- In vitro, Chemical affinity -- Analysis, Alzheimer's disease -- Research, Biological sciences, Chemistry
Abstract

The binding assay measuring the affinities of small molecules for beta-amyloid peptide suggests that the ligands showing greater affinity for the peptide alter peptide aggregation leading to inhibition of cell toxicity. Data also suggest that the affinity of ligands is directly related to their ability to inhibit the cellular toxicity of beta-amyloid.

Published
2002

21. Profile of changes in lipid bilayer structure caused by beta-amyloid peptide

Author

Kremer, John J., Sklansky, Daniel J., and Murphy, Regina M.

Subjects
Biochemistry -- Research, Peptides -- Physiological aspects, Phospholipids -- Physiological aspects, Anions -- Physiological aspects, Cations -- Physiological aspects, Anisotropy -- Analysis, Biological sciences, Chemistry
Abstract

Research has been conducted on the beta-amyloid peptide, a constituent of the senile plagues. Results indicate that A(beta) aggregates increase the steady-state anisotropy of 1,6-diphenyl-1,3,5-hexatriene embedded in the membrane hydrophobic center in phospholipids with anionic, cationic and zwitterionic headgroups.

Published
2001

22. Structure-function relationships for inhibitors of beta-amyloid toxicity containing the recognition sequence KLVFF

Author

Lowe, Tao L., Strzelec, Andrea, Kiessling, Laura L., and Murphy, Regina M.

Subjects
Biochemistry -- Research, Amyloid beta-protein -- Research, Alzheimer's disease -- Causes of, Toxicity testing -- Analysis, Peptides -- Research, Biological sciences, Chemistry
Abstract

Research has been conducted on the beta-amyloid A(beta) protein which is the primary component of Alzheimer's plague. The strategy that has been developed to generate the compounds inhibiting A(beta) toxicity is described.

Published
2001

24. Correlation of beta-amyloid aggregate size and hydrophobicity with decreased bilayer fluidity of model membranes

Author

Kremer, John J., Pallitto, Monica M., Sklansky, Daniel J., and Murphy, Regina M.

Subjects
Cytochemistry -- Research, Amyloid beta-protein -- Physiological aspects, Alzheimer's disease -- Physiological aspects, Cells -- Permeability, Cell membranes -- Physiological aspects, Neurons -- Physiological aspects, Brain -- Physiological aspects, Bilayer lipid membranes -- Physiological aspects, Membrane proteins -- Physiological aspects, Anisotropy -- Physiological aspects, Biological sciences, Chemistry
Abstract

The correlation of beta-amyloid (A-beta) aggregate size and hydrophobicity with lower bilayer fluidity of model membranes has been investigated. The effect of A-beta on anisotropy of DPH embedded in large unilamellar vesicles of pure 1-palmitol-2-oleoyl phosphatidylcholine and 1-palmitoyl-2-oleoyl phosphatidylglycerol as well as in vesicles composed of mixtures of phospholipids, gangliosides, and cholesterol that more nearly mimic neuronal membranes was tested. Self-association of A-beta monomers into aggregates exposes hyhdrophobic sites. It also brings a decrease in membrane fluidity. A-beta aggregate-induced changes in properties of membranes may have negative consequences on functions of cells.

Published
2000

25. Recognition sequence design for peptidyl modulators of beta-amyloid aggregation and toxicity

Author

Pallitto, Monica M., Ghanta, Jyothi, Heinzelman, Peter, Kiessling, Laura L., and Murphy, Regina M.

Subjects
Amyloidosis -- Research, Alzheimer's disease -- Research, Lysine -- Research, Biological sciences, Chemistry
Abstract

A study was conducted to analyze the design requirements of A-beta recognition and the necessity and function of the lysine hexamer disrupting element. The purity and identity of peptides were evaluated by amino acid analysis. Results indicated the effectiveness of coupling recognition with disrupting elements in creating A-beta inhibitors. Findings also suggested that the prevention of A-beta aggregation may not be required for toxicity prevention.

Published
1999

30. Effect of beta-amyloid block of the fast-inactivating K+ channel on intracellular Ca2+ and excitability in a modeled neuron

Author

Good, Theresa A. and Murphy, Regina M.

Subjects
Alzheimer's disease -- Genetic aspects, Neuropeptides -- Physiological aspects, Amyloidosis -- Genetic aspects, Potassium channels -- Physiological aspects, Calcium ions -- Physiological aspects, Neurons -- Physiological aspects, Science and technology
Abstract

[Beta]-Amyloid peptide (A[Beta]), one of the primary protein components of senile plaques found in Alzheimer disease, is believed to be toxic to neurons by a mechanism that may involve loss of intracellular calcium regulation. We have previously shown that A[Beta] blocks the fast-inactivating potassium (A) current. In this work, we show, through the use of a mathematical model, that the A[Beta]-mediated block of the A current could result in increased intracellular calcium levels and increased membrane excitability, both of which have been observed in vitro upon acute exposure to A[Beta]. Simulation results are compared with experimental data from the literature; the simulations quantitatively capture the observed concentration dependence of the neuronal response and the level of increase in intracellular calcium.

Published
1996

33. Transthyretin as both a Sensor and a Scavenger of β-Amyloid Oligomers

Author

Yang, Dennis T., Joshi, Gururaj, Cho, Patricia Y., Johnson, Jeffrey A., and Murphy, Regina M.

Abstract

Transthyretin (TTR) is a homotetrameric transport protein, assembled from monomers that each contain two four-stranded β-sheets and a short α-helix and loop. In the tetramer, the “inner” β-sheet forms a hydrophobic pocket while the helix and loop are solvent-exposed. β-Amyloid (Aβ) aggregates bind to TTR, and the level of binding is significantly reduced in mutants L82A (on the loop) and L110A (on the inner β-sheet). Protection against Aβ toxicity was demonstrated for wild-type TTR but not L82A or L110A, providing a direct link between TTR–Aβ binding and TTR-mediated cytoprotection. Protection is afforded at substoichiometric (1:100) TTR:Aβ molar ratios, and the level of binding of Aβ to TTR is highest for partially aggregated materials and decreased for freshly prepared or heavily aggregated Aβ, suggesting that TTR binds selectively to soluble toxic Aβ aggregates. A novel technique, nanoparticle tracking, is used to show that TTR arrests Aβ aggregation by both preventing formation of new aggregates and inhibiting growth of existing aggregates. TTR tetramers are normally quite stable; tetrameric structure is necessary for the protein’s transport functions, and mutations that decrease tetramer stability have been linked to TTR amyloid diseases. However, TTR monomers bind more Aβ than do tetramers, presumably because the hydrophobic inner sheet is solvent-exposed upon tetramer disassembly. Wild-type and L110A tetramers, but not L82A, were destabilized upon being co-incubated with Aβ, suggesting that binding of Aβ to L82 triggers tetramer dissociation. Taken together, these results suggest a novel mechanism of action for TTR: the EF helix/loop “senses” the presence of soluble toxic Aβ oligomers, triggering destabilization of TTR tetramers and exposure of the hydrophobic inner sheet, which then “scavenges” these toxic oligomers and prevents them from causing cell death.

Published
2024
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37. Characterization of the interaction of [beta]-amyloid with transthyretin monomers and tetramers

Author

Jiali Du and Murphy, Regina M.

Subjects
Amyloid beta-protein -- Structure, Amyloid beta-protein -- Chemical properties, Electron microscopes -- Usage, Gene mutations -- Analysis, Scattering (Physics) -- Analysis, Biological sciences, Chemistry
Abstract

The interaction of [beta]-amyloid ([beta]A) with wild-type (wt) transthyretin (TTR) as well as two mutants, F87M/L110M, engineered to be a stable monomer, and T119M, a naturally occurring mutant with a tetrameric stability higher than that of the wild type is examined. Light scattering and electron microscopy studies have shown that the outcome of the TTR-A[beta] interaction has depended on TTR quaternary structure.

Published
2010

38. Reconsidering the mechanism of polyglutamine peptide aggregation

Author

Lee, Christine C., Walters, Robert H., and Murphy, Regina M.

Subjects
Glutamine -- Chemical properties, Huntington's chorea -- Research, Peptides -- Chemical properties, Protein folding -- Research, Biological sciences, Chemistry
Abstract

The results from measurement of the aggregation kinetics of the polyglutamine peptide [K.sub.2][Q.sub.23][K.sub.2] are presented. Substantial organization of the peptide into soluble linear aggregates is observed during the lag time in sedimentation kinetics.

Published
2007

39. Kinetics of inhibition of beta-amyloid aggregation by transthyretin

Author

Lin Liu and Murphy, Regina M.

Subjects
Alzheimer's disease -- Research, Amyloid beta-protein -- Research, Proteolysis -- Analysis, Biological sciences, Chemistry
Abstract

Results of the biophysical analysis of A(beta) aggregation kinetics in the presence of transthyretin are presented. The findings support a hypothesis wherein transthyretin preferentially binds to aggregated rather than monomeric A(beta), hampering the growth of the aggregates.

Published
2006

46. Insights into the molecular mechanism of protein native-like aggregation upon methylglyoxal glycation

Author

Oliveira, Luís M. A., Gomes, Ricardo A., Yang, Dennis, Família, Carlos, Lages, Ana, Coelho, Ana V., Murphy, Regina M., and Quintas, Alexandre

Subjects
Glycation, Methylglyoxal, Cytochrome c, Native-like aggregation, Conformational diseases
Abstract

“NOTICE: this is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. Volume 1834, Issue 6, June 2013, Pages 1010–1022, DOI 10.1016/j.bbapap.2012.12.001" "Protein glycation induces structural and stability changes that impair protein function, and is associated with several human neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and Familial Amyloidotic Polyneuropathy. Recently we have shown that methylglyoxal induces and stabilizes the formation of small native-like aggregates in the amyloidogenic protein insulin and the same was previously shown for α-synuclein. However, the fundamental biophysical mechanism underlying such methylglyoxal-induced protein aggregation is not yet fully understood. In this study, we used the model protein cytochrome c to characterize the specific glycation targets and to investigate the glycation effects on protein structure, stability and aggregation. Methylglyoxal was found modify cytochrome c in a single residue and to induce the formation of cytochrome c native-like aggregates. Additionally, it is shown that methylglyoxal glycation of cytochrome c also results in the formation of a partially unfolded species. Interestingly, the formation of this partially unfolded species is not implicated in the aggregation process, a clear difference from amyloid fibril mechanisms that involve partially or totally unfolded intermediates. Equilibrium-unfolding experiments using guanidinium hydrochloride shows that glycation strongly reduces cytochrome c conformational stability. This reduction is balanced by aggregation that increases conformational stability. The data collected from analytical and spectroscopic techniques along with kinetic analysis based on least-squares parameter fitting and statistical model discrimination permitted the proposal of a comprehensive thermodynamic and kinetic model for native-like aggregation of methylglyoxal glycated cytochrome c."

Published
2013

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