A5005244112- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Chemical Synthesis and Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Marine Sponges and Natural Products
- Synthetic Organic Chemistry Methods
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Nerve injury and regeneration
- Immune Response and Inflammation
- Invertebrate Immune Response Mechanisms
- Multicomponent Synthesis of Heterocycles
- Nuclear Receptors and Signaling
- Cannabis and Cannabinoid Research
- Neuroscience and Neural Engineering
- Phytase and its Applications
- Oxidative Organic Chemistry Reactions
- Marine Toxins and Detection Methods
- Glycosylation and Glycoproteins Research
- Pharmacological Receptor Mechanisms and Effects
- Influenza Virus Research Studies
- Synthesis and Catalytic Reactions
- Pain Mechanisms and Treatments
- Antimicrobial Peptides and Activities
Bristol-Myers Squibb (United States)
2022
Bristol-Myers Squibb (Germany)
2014
Northwestern University
2008-2012
Eli Lilly (United States)
2010-2011
Abstract Activation of NMDA receptors (NMDAR) in the hippocampus is essential for formation contextual and trace memory. However, role individual NMDAR subunits molecular mechanisms contributing to these memory processes not known. Here we demonstrate, using intrahippocampal injection subunit‐selective compounds, that NR2A‐preferring antagonist impaired fear conditioning as well learning‐induced increase nuclear protein c‐Fos. The NR2B‐specific antagonist, on other hand, selectively blocked...
Neuronal AMPA receptor complexes comprise a tetramer of GluA pore-forming subunits as well accessory components, including transmembrane regulatory proteins (TARPs) and cornichon-2/3 (CNIH-2/3). The mechanisms that control complex assembly remain unclear. responses in neurons differ from those cell lines transfected with plus TARPs γ-8 or γ-7, which show unusual resensitization kinetics non-native pharmacologies. Using tandem GluA/TARP constructs to constrain stoichiometry, we here these...
Abstract A highly regioselective domino metathesis reaction of 7‐oxanorbornene was developed that employed an intramolecular association amide carbonyl group to a ruthenium metal centre. By using this reaction, twelve glutamate analogues inspired by dysiherbaine were efficiently synthesized over 12–14 steps; one the exhibited bioactivity consistent with central nervous system depression.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Abstract Transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits that modulate trafficking, gating and pharmacology throughout the brain. Why cornichon‐2 (CNIH‐2), another receptor‐associated protein, modulates in hippocampal neurons but not cerebellar granule remains unresolved. Here, we report CNIH‐2 differentially impacts Type‐Ia (γ‐2 or γ‐3) vs. Type‐Ib (γ‐4 γ‐8) TARP‐containing receptors. Specifically, with receptors comprising γ‐2, cerebellar‐enriched TARP...
Tau is a microtubule-associated protein (MAPT, tau) implicated in the pathogenesis of tauopathies, spectrum neurodegenerative disorders characterized by accumulation hyperphosphorylated, aggregated tau. Because tau pathology can be distinct across diseases, pragmatic therapeutic approach may to intervene at level transcript, as it makes no assumptions mechanisms toxicity. Here we performed large library screen locked-nucleic-acid (LNA)-modified antisense oligonucleotides (ASOs), where...
In this article a regioselective domino metathesis reaction of unsymmetrical 7-oxanorbornenes, readily available by tandem Ugi/Diels-Alder as key step, promoted the Hoveyda-Grubbs second-generation catalyst in presence electron-rich vinyl acetate cross (CM) substrate is reported. The mechanism for unusually high regioselectivity observed CM was investigated, and course where Fischer-type carbene ["Ru"= CH(OAc)] generates steric interaction proposed. products were further converted to four...
Tau-tubulin kinase 1 (TTBK1) is a dual-specificity (serine/threonine and tyrosine) belonging to the casein superfamily. TTBK1 neuron-specific that regulates tau phosphorylation. Hyperphosphorylation of implicated in pathogenesis Alzheimer's disease. Two kinase-domain constructs were expressed baculovirus-infected insect-cell system purified. The purified proteins crystallized using hanging-drop vapor-diffusion method. X-ray diffraction data collected structure was determined by molecular...
Marine organisms have yielded a variety of metabolites with neuropharmacological applications. Here we describe the isolation and pharmacological characterization four novel, neurologically active purines 1−4, isolated from Haplosclerida sponges collected in Republic Palau. The structures were determined by analyses spectral X-ray data. Compound 1 induced convulsions upon intracerebroventricular injection into mice, CD50 value 2.4 nmol/mouse. Purines 2−4 mouse bioassays at higher doses....
Abstract A novel family of functionalized peptide toxins, aculeines (ACUs), was isolated from the marine sponge Axinyssa aculeate. ACUs are polypeptides with N‐terminal residues that modified by addition long‐chain polyamines (LCPA). Aculeines were present in extract as a complex mixture differing polyamine chain lengths and structures. ACU‐A B, which purified this study, share common polypeptide but differ their residue modifications. The amino acid sequence portion B deduced 3′ 5′ RACE,...
AMPA receptors mediate fast excitatory transmission in the brain. Neuronal comprise GluA pore-forming principal subunits and can associate with multiple modulatory components, including transmembrane receptor regulatory proteins (TARPs) CNIHs (cornichons). potentiators non-competitive antagonists represent potential targets for a variety of neuropsychiatric disorders. Previous studies showed that antagonist GYKI-53655 displaces binding potentiator from brain but not recombinant subunits....
NPT520-34 is a clinical stage, small molecule being developed for the treatment of Parkinson's disease and other neurodegenerative disorders. The therapeutic potential was first suggested by findings from cell-based assays alpha-synuclein clearance. As reported here, subsequently evaluated therapeutically relevant actions in transgenic animal model that overexpresses human an acute lipopolysaccharide-challenge using wild-type mice. Daily administration to mThy1-alpha-synuclein (Line 61) mice...
Toll-like receptors (TLRs) play a critical role in innate immune system responses to damage-associated molecular patterns (DAMPs) and pathogen-associated (PAMPs). A growing body of evidence suggests that excessive TLR-mediated activation can lead neuronal damage precipitate or perpetuate neurodegenerative diseases. Among TLR subtypes, both TLR2 TLR9 have been implicated disorders with increased expression these the central nervous being associated pro-inflammatory signaling burdens...
N‐ glycans covalently attached to integral membrane proteins on neurons act as a reservoir for considerable structural diversity and represent potential sites of modulation by oligosaccharide‐binding known lectins. We found that galectins, family galactose‐binding lectins, allosteric modulators ionotropic glutamate receptors (iGluRs) engage signaling pathways lead alterations in dendritic structure. These could potentially impact synaptic transmission likely have diverse effects neuronal the...