A5043215626- Alzheimer's disease research and treatments
- Chemical Synthesis and Analysis
- Spacecraft and Cryogenic Technologies
- Space Exploration and Technology
- Cholinesterase and Neurodegenerative Diseases
- Synthesis of β-Lactam Compounds
- Autophagy in Disease and Therapy
- Integrated Circuits and Semiconductor Failure Analysis
- Synthesis of heterocyclic compounds
- Synthesis and Catalytic Reactions
- Computational Drug Discovery Methods
- Spaceflight effects on biology
- Folate and B Vitamins Research
- Synthetic Organic Chemistry Methods
- Spacecraft Design and Technology
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Neuroscience and Neuropharmacology Research
- Inflammatory mediators and NSAID effects
- Asthma and respiratory diseases
- Epigenetics and DNA Methylation
- Synthesis and Reactions of Organic Compounds
- Planetary Science and Exploration
- Asymmetric Synthesis and Catalysis
- Synthesis and Biological Evaluation
Baylor College of Medicine
2019-2024
Humboldt State University
2018-2022
AstraZeneca (Sweden)
2015-2021
The University of Texas at Austin
2019-2021
Loughborough University
2004-2017
AstraZeneca (United Kingdom)
2009-2017
James J. Peters VA Medical Center
2010-2016
Sanford Consortium for Regenerative Medicine
2016
University of California, San Diego
2016
University of Toyama
2016
Presenilin 1 (PSEN1) encodes the catalytic subunit of γ-secretase, and PSEN1 mutations are most common cause early onset familial Alzheimer's disease (FAD). In order to elucidate pathways downstream PSEN1, we characterized neural progenitor cells (NPCs) derived from FAD mutant subjects. Thus, generated induced pluripotent stem (iPSCs) affected unaffected individuals two families carrying mutations. fibroblasts, NPCs produced greater ratios Aβ42 Aβ40 relative their control counterparts, with...
SorCS1 and SorL1/SorLA/LR11 belong to the sortilin family of vacuolar protein sorting-10 (Vps10) domain-containing proteins. Both are genetically associated with Alzheimer's disease (AD), SORL1 expression is decreased in brains patients suffering from AD. SORCS1 also types 1 2 diabetes mellitus (T1DM, T2DM). We have undertaken a study possible role(s) for metabolism amyloid-β peptide (Aβ) Aβ precursor (APP), test hypothesis that Sorcs1 deficiency might be common genetic risk factor...
Recent evidence suggests that high molecular weight soluble oligomeric Abeta (oAbeta) assemblies (also known as Abeta-derived diffusible ligands, or ADDLs) may represent a primary neurotoxic basis for cognitive failure in Alzheimer disease (AD). To date, most vivo studies of oAbeta/ADDLs have involved injection purified from the cerebrospinal fluid human subjects with AD conditioned media Abeta-secreting cells into experimental animals. We sought to study bioactivities endogenously formed...
Proteins secreted by strains of Mycobacterium tuberculosis during short-term, zinc-sufficient batch culture were identified in order to define antigens likely be relevant the pathogenesis human disease. [35S]Methionine-labelled proteins supernatants 4-7 d cultures separated PAGE under both denaturing and non-denaturing conditions, position labelled material was determined. Secreted protein patterns M. quite similar those Bacillus Calmette-Guérin (BCG) but differed absence 46 kDa dimeric...
Alzheimer disease (AD) is a form of neurodegeneration that develops over the course multiple decades and as result accumulation pathogenic amyloid-β (Aβ) peptide, also known A4. In late-stage AD, failure autophagic clearance results in neuronal cell bodies are almost entirely consumed by vacuoles (AVs). Previously, we have shown potential AD drug latrepirdine (aka Dimebon(®)), Russian antihistamine has mixed phase II clinical trials regulates metabolism amyloid-β/A4 precursor protein (APP)....
Optimal functioning of neuronal networks is critical to the complex cognitive processes memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular animal models as well human biospecimens show AD-related stressors mediate global disturbances dynamic intra- inter-neuronal through pathologic rewiring chaperome system into epichaperomes. These structures provide backbone upon which proteome-wide connectivity, turn, protein become disturbed ultimately...
The roots of Cryptolepis sanguinolenta have been investigated for their chemical composition since 1931 but so far no studies on the leaves reported although they are used in traditional medicine Guinea-Bissau. Two new alkaloids identified as cryptolepinoic acid (1) and methyl cryptolepinoate (2) known cryptolepine (4), hydroxycryptolepine (5/5a) quindoline (6), were isolated from ethanolic chlorophormic leaf extracts. Aqueous extracts seven those tested vitro against Plasmodium falciparum...
A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3-aminocrotonamides 3-aminocrotonate esters. Structure-activity relationships were evaluated where PAF measured in vitro determining concentration compound (IC50) required to inhibit PAF-induced...
Latrepirdine (Dimebon™), an anti-histamine, has shown some benefits in trials of neurodegenerative diseases characterized by accumulation aggregated or misfolded protein such as Alzheimer's disease (AD) and been to promote the removal
Proneurogenic compounds have recently shown promise in some mouse models of Alzheimer's pathology. Antagonists at Group II metabotropic glutamate receptors (Group mGluR: mGlu2, mGlu3) are reported to stimulate neurogenesis. Agonists those trigger γ-secretase-inhibitor-sensitive biogenesis Aβ42 peptides from isolated synaptic terminals, which is selectively suppressed by antagonist pretreatment. We assessed the therapeutic potential chronic pharmacological inhibition mGluR Dutch APP...
A class of potent, nonsteroidal, selective indazole ether-based glucocorticoid receptor modulators (SGRMs) was developed for the inhaled treatment respiratory diseases. Starting from an orally available compound with demonstrated anti-inflammatory activity in rat, a soft-drug strategy implemented to ensure rapid elimination drug candidates minimize systemic GR activation. The first clinical candidate 1b (AZD5423) displayed potent inhibition lung edema rat model allergic airway inflammation...
Recent studies have implicated specific assembly subtypes of β-amyloid (Aβ) peptide, specifically soluble oligomers (soAβ) as disease-relevant structures that may underlie memory loss in Alzheimer disease. Removing existing and insoluble Aβ assemblies is thought to be essential for any attempt at stabilizing brain function slowing cognitive decline IV immunoglobulin (IVIg) therapies been shown contain naturally occurring polyclonal antibodies recognize conformational neoepitopes or including...
ABSTRACT Alzheimer's disease (AD) is a complex and slowly progressing dementing disorder that results in neuronal synaptic loss, deposition brain of aberrantly folded proteins, impairment spatial episodic memory. Most studies mouse models AD have employed analyses cognitive status assessment amyloid burden, gliosis, molecular pathology during progression. Here we sought to understand the behavioral, cellular, ultrastructural, changes occur at pathological stage equivalent early stages human...