Site-specific modification of Candida antarctica lipase B via residue-specific incorporation of a non-canonical amino acid.

In order to modify proteins in a controlled way, new functionalities need to be introduced in a defined manner. One way to accomplish this is by the incorporation of a non-natural amino acid of which the side chain can selectively be reacted to other molecules. We have investigated whether the relatively simple method of residue-specific replacement of methionine by azidohomoalanine can be used to achieve monofunctionalization of the model enzyme Candida antarctica lipase B.

Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse model.

When given orally to a transgenic mouse model of Alzheimer disease, cyclohexanehexol stereoisomers inhibit aggregation of amyloid beta peptide (Abeta) into high-molecular-weight oligomers in the brain and ameliorate several Alzheimer disease-like phenotypes in these mice, including impaired cognition, altered synaptic physiology, cerebral Abeta pathology and accelerated mortality. These therapeutic effects, which occur regardless of whether the compounds are given before or well after the onset of the Alzheimer disease-like phenotype, support the idea that the accumulation of Abeta oligomers has a central role in the pathogenesis of Alzheimer disease.

Biophysical characterization of longer forms of amyloid beta peptides: possible contribution to flocculent plaque formation.

Alzheimer's disease is characterized by amyloid deposits in the parenchyma and vasculature of the brain. The plaques are mainly composed of amyloid beta (Abeta) peptides ending in residues 40 and 42. Novel longer Abeta peptides were found in brain homogenates of mouse models of Alzheimer's disease and human brain tissue of patients carrying the familial amyloid precursor protein V717F mutation.

Ciglitazone increases basal cytokine expression in the central nervous system of adult rats.

Ciglitazone, rosiglitazone, and pioglitazone belong to a relatively new class of antidiabetic agents referred to as thiazolidinediones (TZDs). Later, TZDs were found to be peroxisome proliferator-activated receptor (PPAR)-gamma agonists and to elicit anti-inflammatory effects in both in vitro and in vivo models in response to stimuli such as lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA). In the present study, we sought to investigate the effects of oral administration of ciglitazone on basal inflammatory cytokine expression in healthy adult rats.

UBA1 and UBA2, two proteins that interact with UBP1, a multifunctional effector of pre-mRNA maturation in plants.

Nicotiana plumbaginifolia UBP1 is an hnRNP-like protein associated with the poly(A)(+) RNA in the cell nucleus. Consistent with a role in pre-mRNA processing, overexpression of UBP1 in N. plumabaginifolia protoplasts enhances the splicing of suboptimal introns and increases the steady-state levels of reporter mRNAs, even intronless ones.