Rockville, MD, United States
Rockville, MD, United States
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Charkhkar H.,George Mason University | Meyyappan S.,George Mason University | Matveeva E.,Adlyfe Inc. | Moll J.R.,Adlyfe Inc. | And 4 more authors.
Brain Research | Year: 2015

In vitro assays offer a means of screening potential therapeutics and accelerating the drug development process. Here, we utilized neuronal cultures on planar microelectrode arrays (MEA) as a functional assay to assess the neurotoxicity of amyloid-β 1-42 (Aβ42), a biomolecule implicated in the Alzheimer's disease (AD). In this approach, neurons harvested from embryonic mice were seeded on the substrate-integrated microelectrode arrays. The cultured neurons form a spontaneously active network, and the spiking activity as a functional endpoint could be detected via the MEA. Aβ42 oligomer, but not monomer, significantly reduced network spike rate. In addition, we demonstrated that the ionotropic glutamate receptors, NMDA and AMPA/kainate, play a role in the effects of Aβ42 on neuronal activity in vitro. To examine the utility of the MEA-based assay for AD drug discovery, we tested two model therapeutics for AD, methylene blue (MB) and memantine. Our results show an almost full recovery in the activity within 24 h after administration of Aβ42 in the cultures pre-treated with either MB or memantine. Our findings suggest that cultured neuronal networks may be a useful platform in screening potential therapeutics for Aβ induced changes in neurological function. © 2015 Elsevier B.V.


Matveeva E.G.,University of Maryland Baltimore County | Matveeva E.G.,Adlyfe Inc. | Rudolph A.,Adlyfe Inc. | Moll J.R.,Adlyfe Inc. | Thompson R.B.,University of Maryland Baltimore County
ACS Chemical Neuroscience | Year: 2012

Amyloid β (Abeta) peptides in their oligomeric form have been proposed as major toxic species in Alzheimers disease (AD). There are a limited number of anti-Abeta antibodies specific to oligomeric forms of Abeta compared to the monomeric form, and accurate measurement of oligomeric forms in biological samples, cerebrospinal fluid (CSF), or brain extracts remains challenging. We introduce an oligomerspecific (in preference to monomers or fibrils) fluorescence assay based on a conformationally sensitive bis-pyrene-labeled peptide that contains amino acid residues 16-35 of the human amyloid beta protein (pronucleon peptide, PP). This peptide exhibits a shift in fluorescence emission from pyrene excimer to pyrene monomer emission resulting from a conformational change. Specific binding of PP to oligomeric forms of Abeta can be monitored in solution by a change in fluorescence spectrum as well as a change in pyrene monomer fluorescence anisotropy (or polarization). The mechanism of binding and its relation to anisotropy and fluorescence lifetime changes are discussed. The development of a simple, rapid, anisotropy assay for measurement of Abeta oligomers is important for further study of the oligomers role in AD, and specific detection of oligomers in biological samples, such as cerebrospinal fluid. © 2012 American Chemical Society.


Nyborg A.C.,Adlyfe Inc. | Moll J.R.,Adlyfe Inc. | Wegrzyn R.D.,Adlyfe Inc. | Havas D.,JSW Life science GmbH | And 3 more authors.
Journal of Alzheimer's Disease | Year: 2013

Accumulation of amyloid-β (Aβ) cascade aggregates is considered a hallmark of Alzheimer's disease (AD). Current dogma holds that the appearance of Aβ oligomers and larger aggregates occur many years prior to plaque formation associated with the advanced and irreparable neurocognitive decline characteristic of AD. This premise is the impetus to identify these Aβ precursor structures prior to advanced plaque development. The Pronucleon™ technology platform is comprised of a novel series of engineered peptides that provide a unique readout when associated with beta-rich fiber and oligomeric Aβ. This technology has been applied to Ex Vivo tissue sections and In Vivo mouse models of AD to determine the potential utility of these synthetic peptides as potential imaging agents. In Ex Vivo studies, the Pronucleon™ peptide binds plaque like structures in brain sections obtained from transgenic mice overexpressing hAPP with both the human Swedish and London Aβ mutations. In Vivo, Pronucleon™ peptide administered peripherally can localize to the brain and label plaques throughout the brain in transgenic mice. Taken together, the data suggest that Pronucleon™ could provide a new imaging tool for Aβ cascade elements that precede advanced plaque and fibril formation, thereby advancing early diagnosis and treatment opportunities. © 2013 - IOS Press and the authors. All rights reserved.


Patent
Adlyfe Inc. | Date: 2014-06-05

Described are methods for the detection, in the eye of an individual, of protein aggregates or other misfolded proteins associated with disease using peptide or peptide mimic probes that preferentially associate with the protein aggregates or misfolded proteins, which can be accomplished non-invasively.


Patent
Adlyfe Inc. | Date: 2014-09-12

The invention provides methods and kits for detecting conformationally altered proteins and prions in a sample. In one embodiment, the conformationally altered proteins and prions are associated with amyloidogenic diseases.


Patent
Adlyfe Inc. | Date: 2011-04-20

The invention provides methods and kits for detecting conformationally altered proteins and prions in a sample. In one embodiment, the conformationally altered proteins and prions are associated with amyloidogenic diseases.


The present invention provides methods of making immobilized probes that are specific for prion proteins, methods of using such probes to bind, detect, and remove prion proteins from samples, and kits for practicing the invention. The invention discloses immobilized probes that are locked into a particular, pre-determined configuration and that retain their activity and specificity even when exposed to conditions that would typically alter their activity and specificity.


Patent
Adlyfe Inc. | Date: 2014-06-09

Disclosed are novel peptides that are useful, for example, for detecting target proteins having a -sheet secondary structure which may be associated with a disease, and for diagnosing and treating such a disease. Related methods and kits also are disclosed.


PubMed | Inc. SoSACorp, Adlyfe Inc. and George Mason University
Type: | Journal: Brain research | Year: 2015

In vitro assays offer a means of screening potential therapeutics and accelerating the drug development process. Here, we utilized neuronal cultures on planar microelectrode arrays (MEA) as a functional assay to assess the neurotoxicity of amyloid- 1-42 (A42), a biomolecule implicated in the Alzheimers disease (AD). In this approach, neurons harvested from embryonic mice were seeded on the substrate-integrated microelectrode arrays. The cultured neurons form a spontaneously active network, and the spiking activity as a functional endpoint could be detected via the MEA. A42 oligomer, but not monomer, significantly reduced network spike rate. In addition, we demonstrated that the ionotropic glutamate receptors, NMDA and AMPA/kainate, play a role in the effects of A42 on neuronal activity in vitro. To examine the utility of the MEA-based assay for AD drug discovery, we tested two model therapeutics for AD, methylene blue (MB) and memantine. Our results show an almost full recovery in the activity within 24h after administration of A42 in the cultures pre-treated with either MB or memantine. Our findings suggest that cultured neuronal networks may be a useful platform in screening potential therapeutics for A induced changes in neurological function.


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