Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone.

Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin.

Biochemical and behavioral characterization of the double transgenic mouse model (APPswe/PS1dE9) of Alzheimer's disease.

OBJECTIVE The double transgenic mouse model (APPswe/PS1dE9) of Alzheimer's disease (AD) has been widely used in experimental studies. β-Amyloid (Aβ) peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model.

pKa-dependent formation of amides in water from an acyl phosphate monoester and amines.

Acyl phosphate monoesters are readily prepared biomimetically activated anionic derivatives of carboxylic acids that react rapidly with amines in water to form amides. A plot of the logarithms of the rate constants for the reactions of a series of primary amines with benzoyl methyl phosphate depends on the pKa of the conjugate acids of the amines (beta(nuc) approximately 0.9).

3-Substituted imidazo[1,2-d][1,2,4]-thiadiazoles: a novel class of factor XIIIa inhibitors.

A new class of selective FXIIIa inhibitors with a bicyclic [1,2,4]-thiadiazole pharmacophore is described. At 160 muM, compound 8 caused 50% reduction in fibrin gamma-chain cross-linking and suppressed the polymerization of alpha chains in platelet-depleted human plasma clots. Fibrinolysis rates in response to tissue plasminogen activator were directly proportional to the concentration of 8 in plasma at the time of clotting.

Transglutaminases as targets for pharmacological inhibition.

Transglutaminases (TGases), a family of enzymes that catalyze the formation of epsilon-(gamma-glutamyl)lysine isopeptide linkage, play an important physiological role in hemostasis, wound healing, assembly and remodeling of the extracellular matrix, cell signaling and apoptosis. Although many members of this class of enzymes have been known for decades, their role in various physiological and pathological processes is still a subject of substantial research and debate. Convincing evidence exists that TGases are involved in formation of cytotoxic proteinatious aggregates in Alzheimer's, Huntington's and other neurodegenerative diseases.

1,2,4-thiadiazole: a novel Cathepsin B inhibitor.

A novel class of Cathepsin B inhibitors has been developed with a 1,2,4-thiadiazole heterocycle as the thiol trapping pharmacophore. Several compounds with different dipeptide recognition sequence (i.e.