Validation of folate in a convenient yeast assay suited for identification of inhibitors of Alzheimer's amyloid-beta aggregation.

Previously in the search for chemopreventatives for Alzheimer's disease (AD), microbial cells with amyloid-beta (Abeta) protein fusions have been used to screen for compounds that reduce the aggregation, misfolding or oligomerization of Abeta. In the current study, such a system has been used to look at the effect of folate, whose deficiency has been associated with AD. A folate-deficient yeast strain producing Abeta fused to green fluorescent protein (GFP) that spontaneously misfolds/aggregates and suppresses green fluorescence was used to examine the effects of folinic acid on Abeta-GFP fluorescence.

Variation in the gene coding for the M5 muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction: evidence from a prospective population based cohort study of young adults.

Background: The mesolimbic structures of the brain are important in the anticipation and perception of reward. Moreover, many drugs of addiction elicit their response in these structures. The M5 muscarinic receptor (M5R) is expressed in dopamine-containing neurones of the substantia nigra pars compacta and ventral tegmental area, and regulates the release of mesolimbic dopamine.

Association between the COMT Val158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health.

Objectives: Catechol-O-methyltransferase plays a central role in the metabolism of biogenic amines such as norepinephrine, dopamine and serotonin. Functional studies have demonstrated a dose relationship between ValMet genotypes and catechol-O-methyltransferase activity. Compared with the ValVal genotype, the ValMet and MetMet genotypes result in two- and four-fold reductions in catechol-O-methyltransferase activity, respectively.

Nicotine dependence in a prospective population-based study of adolescents: the protective role of a functional tyrosine hydroxylase polymorphism.

Dopamine is a key neurotransmitter of the mesolimbic reward pathway in the human brain, and tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis. Consequently, the gene encoding TH is a strong candidate for involvement in the genetic component of addiction. The importance of this gene in nicotine dependence is supported by many studies showing a link between nicotine administration and TH expression.

Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death.

The Free Radical Theory of Aging proposes that reactive oxygen species (ROS) contribute to the pathophysiology of aging. Our previous data highlight the importance of antioxidant enzymes, superoxide dismutase 1 (Sod1) and glutathione peroxidase 1 (Gpx1), in regulating this process. Previously, we demonstrated that a perturbation in the Sod1-to-Gpx1 ratio, as a consequence of Sod1 overexpression, leads to senescence-like changes.