Anne Brown

Learn More
The amyloid β-peptide (Aβ) is a 40-42 residue peptide that is the principal toxic species in Alzheimer's disease (AD). The oxidation of methionine-35 (Met35) to the sulfoxide form (Met35(ox)) has been identified as potential modulator of Aβ aggregation. The role Met35(ox) plays in Aβ neurotoxicity differs among experimental studies, which may be due to(More)
BACKGROUND The ability to perform de novo biosynthesis of purines is present in organisms in all three domains of life, reflecting the essentiality of these molecules to life. Although the pathway is quite similar in eukaryotes and bacteria, the archaeal pathway is more variable. A careful manual curation of genes in this pathway demonstrates the value of(More)
Macromolecular function arises from structure, and many diseases are associated with misfolding of proteins. Molecular simulation methods can augment experimental techniques to understand misfolding and aggregation pathways with atomistic resolution, but the reliability of these predictions is a function of the parameters used for the simulation. There are(More)
Participating in undergraduate research can be a pivotal experience for students in life science disciplines. Development of critical thinking skills, in addition to conveying scientific ideas in oral and written formats, is essential to ensuring that students develop a greater understanding of basic scientific knowledge and the research process.(More)
High performance computing (HPC) is essential in order to perform detailed MD simulations that allow for mechanistic insight into many diseases. Alzheimer's disease (AD) pathology is primarily caused by the Aβ(42) peptide. MD simulations of a toxic (human Aβ(42)) and non-toxic (rat Aβ(42)) were performed in physiologically-relevant membrane(More)
The two isoforms of sphingosine kinase (SphK1 and SphK2) are the only enzymes that phosphorylate sphingosine to sphingosine-1-phosphate (S1P), which is a pleiotropic lipid mediator involved in a broad range of cellular processes including migration, proliferation, and inflammation. SphKs are targets for various diseases such as cancer, fibrosis, and(More)
The hallmark characteristics of plaque formation and neuronal cell death in Alzheimer's disease (AD) are caused principally by the amyloid β-peptide (Aβ). Aβ sequence and lipid composition are essential variables to consider when elucidating the impact of biological membranes on Aβ structure and the effect of Aβ on membrane integrity. Atomistic molecular(More)
Adenine deaminases (Ade) and hypoxanthine/guanine phosphoribosyltransferases (Hpt) are widely distributed enzymes involved in purine salvage. Characterization of the previously uncharacterized Ade (MJ1459 gene product) and Hpt (MJ1655 gene product) are discussed here and provide insight into purine salvage in Methanocaldococcus jannaschii. Ade was(More)
The aggregation cascade and peptide-membrane interactions of the amyloid β-peptide (Aβ) have been implicated as toxic events in the development and progression of Alzheimer's disease. Aβ42 forms oligomers and ultimately plaques, and it has been hypothesized that these oligomeric species are the main toxic species contributing to neuronal cell death. To(More)
Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with its five G-protein coupled receptors (S1P1-5) to regulate cell growth and survival and has been implicated in a variety of diseases including cancer and sickle cell disease. As the key mediators in the synthesis of S1P, sphingosine kinase (SphK) isoforms 1 and 2 have(More)
  • 1