A5051869254- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Computational Drug Discovery Methods
- Supramolecular Self-Assembly in Materials
- Epigenetics and DNA Methylation
- Cholinesterase and Neurodegenerative Diseases
- Point processes and geometric inequalities
- Prion Diseases and Protein Misfolding
- Phosphodiesterase function and regulation
- Neurological Disease Mechanisms and Treatments
- Immune Response and Inflammation
- Phytoestrogen effects and research
- Proteins in Food Systems
- Advanced Glycation End Products research
- Inflammasome and immune disorders
- Inflammation biomarkers and pathways
- Medicinal Plants and Neuroprotection
- Parkinson's Disease Mechanisms and Treatments
- Carbohydrate Chemistry and Synthesis
- Chinese history and philosophy
- Indian and Buddhist Studies
- S100 Proteins and Annexins
- Protein Structure and Dynamics
- Sphingolipid Metabolism and Signaling
- Humor Studies and Applications
University of Missouri–St. Louis
2014-2023
Purdue University West Lafayette
1999-2022
Transylvania University
2009
Mayo Clinic
2005
Jacksonville College
2004
Mayo Clinic in Florida
2001-2004
WinnMed
2004
Johns Hopkins University
2002-2004
Johns Hopkins Medicine
2002
Wilmington University
2001
Abstract The primary molecules for mediating the innate immune response are Toll‐like family of receptors (TLRs). Recent work has established that amyloid‐beta (Aβ) fibrils, components senile plaques in Alzheimer’s disease (AD), can interact with TLR2/4 accessory protein CD14. Using antibody neutralization assays and tumor necrosis factor alpha release human monocytic THP‐1 cell line, we determined both TLR2 TLR4 mediated an inflammatory to aggregated Aβ(1–42). This was contrast exclusive...
Amyloid plaques in brain tissue are a hallmark of Alzheimer's disease. Primary components these 40- and 42-residue peptides, denoted Aβ(1−40) Aβ(1−42), that derived by proteolysis cellular amyloid precursor protein. Synthetic Aβ(1−42) form fibrils vitro share many features with the plaques. Soluble intermediates Aβ fibrillogenesis, termed protofibrils, have been identified previously, here we describe formation isolation protofibrils size exclusion chromatography. In some experiments, was...
The brains of Alzheimer's disease (AD) patients contain large numbers amyloid plaques that are rich in fibrils composed 40- and 42-residue amyloid-beta (Abeta) peptides. Several lines evidence indicate fibrillar Abeta especially soluble aggregates important the etiology AD. Recent reports also stress polymorphic a single polypeptide can fold into multiple conformations. Here we demonstrate Abeta-(1-40) form with predominant beta-structures differ stability morphology. One class involved...
Senile plaques composed of amyloid-β protein (Aβ) are an unshakable feature the Alzheimer's disease (AD) brain. Although there is significant debate on role in AD progression, little disagreement their stimulating a robust inflammatory response within context disease. Significant markers such as activated microglia and cytokines observed almost exclusively surrounding plaques. However, recent evidence suggests that plaque exterior may contain measurable level soluble Aβ aggregates. The...
Prior work suggests that amyloid precursor protein (APP) can function as a proinflammatory receptor on immune cells, such monocytes and microglia. Therefore, we hypothesized APP serves this in microglia during Alzheimer9s disease. Although fibrillar β (Aβ)-stimulated cytokine secretion from both wild-type knock-out (mAPP<sup>−/−</sup>) microglial cultures, oligomeric Aβ was unable to stimulate increased mAPP<sup>−/−</sup> cells. This consistent with an ability of bind APP. Similarly,...
Some of the pathological hallmarks Alzheimer's disease brain are senile plaques composed insoluble amyloid-β protein (Aβ) fibrils. However, much recent emphasis in research has been on soluble Aβ aggregates response to a growing body evidence that shows these species may be more neurotoxic than Within this subset aggregated protofibrils and oligomers. Although each widely investigated separately, few studies have directly compared contrasted their physical properties. In work, we examined...
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding mediate cell-to-cell communication have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types EVs are distinguished by the mechanism cell release their size, with smaller larger MVs ranging from 30 to 100 nm 1 μm diameter, respectively. MV numbers increased AD appear interact amyloid-β peptide (Aβ), primary...
Microglial cells play a critical role in the propagation of neuroinflammation central nervous system. Microglia sense and respond to environmental signals including chemical, physical biological cues from surrounding cell/tissue components. In this project, our goal was examine effects surface texture on BV-2 microglia morphology function by comparing flat nanoporous gold (np-Au) surfaces more conventional glass. The biocompatibility np-Au with evaluated using functional cell assays high...
Accumulation of aggregated amyloid-β peptide (Aβ) in the brain is a pathological hallmark Alzheimer's disease (AD). In vitro studies indicate that 40- to 42-residue Aβ solution will undergo self-assembly leading transient appearance soluble protofibrils and ultimately insoluble fibrils. The amphiphilic accumulates preferentially at hydrophilic/hydrophobic interface. Solid surfaces air−water interfaces have been shown previously promote aggregation, but detailed characterization these...
Aggregation and accumulation of amyloid-β peptide (Aβ) is a key component Alzheimer's disease (AD). While monomeric Aβ appears to be benign, oligomers adopt biologically detrimental structure. These soluble structures can detected in AD brain tissue by antibodies that demonstrate selectivity for aggregated Aβ. Protofibrils are subset oligomeric species described as small (< 100 nm) curvilinear assemblies enriched β-sheet Our own vitro studies microglial cells much more sensitive Aβ42...
A series of isoflavone and tyrphostin compounds were found to inhibit the degradation cAMP by several cyclic nucleotide phosphodiesterase (PDE) isozymes. Specific hydroxyl groups on structure critical for PDE isozyme-selective inhibition. Replacement C-7 group with a methoxy raised IC<sub>50</sub> PDE1, PDE3, PDE4. The absence C-5 IC<sub>50</sub>from 5 >100 μM PDE4, but actually lowered PDE3 PDE1. C-4′ yet only slightly changed Various tyrphostins also potent inhibitors four-carbon side...
Nordihydroguaiaretic acid (NDGA) was observed by Ono et al. (J Neurochem 87:172-181, 2002) to decrease the fluorescence of thioflavin T associated with freshly extended amyloid beta-protein (Abeta) fibrils. They concluded that NDGA could disaggregate Abeta fibrils into aggregates were larger than monomers or oligomers and did not bind T. Such an effect be therapeutic importance in treatment Alzheimer's disease. In current study, we confirmed induces a Abeta(1-40) this observation...
J. W. Suggs, M. Dube and Nichols, Chem. Soc., Commun., 1993, 307 DOI: 10.1039/C39930000307
The β-site amyloid precursor protein-cleaving enzyme (BACE) cleaves the protein to produce N terminus of β peptide, a major component plaques found in brains Alzheimer9s disease patients. Sequence analysis BACE indicates that contains consensus sequences most known aspartyl proteases, but otherwise has only modest homology with proteases three-dimensional structure (i.e., pepsin, renin, or cathepsin D). Because been shown be one two proteolytic activities responsible for production Aβ this...