Simvastatin inhibits protein isoprenylation in the brain

Evidence suggests that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, may reduce the risk of Alzheimer's disease (AD). Statin action in patients with AD, as in those with heart disease, is likely to be at least partly independent of the effects of statins on cholesterol. Statins can alter cellular signaling and protein trafficking through inhibition of isoprenylation of Rho, Cdc42, and Rab family GTPases. The effects of statins on protein isoprenylation in vivo, particularly in the central nervous system, are poorly studied. We utilized two-dimensional gel electrophoresis approaches to directly monitor the levels of isoprenylated and non-isoprenylated forms of Rho and Rab family GTPases. We report that simvastatin significantly inhibits RhoA and Rab4, and Rab6 isoprenylation at doses as low as 50 nM in vitro. We also provide the first in vivo evidence that statins inhibit the isoprenylation of RhoA in the brains of rats and RhoA, Cdc42, and H-Ras in the brains of mice treated with clinically relevant doses of simvastatin

The impact of general and carbon-related environmental knowledge on attitudes and behaviour of US consumers

Global warming and carbon emissions have gained international attention. However, it would appear that consumers are still unclear about what it encompasses and how it relates to their individual behaviour. Using the Theory of Reasoned Action (TRA) as a guiding framework, this study presents a structural equation model that tests the relationships between carbon and environmental knowledge, environmental attitude and behaviour using a sample of US consumers. The findings of the research suggest that a positive relationship was found between general and carbon-specific knowledge, attitude towards the environment, and general and carbon-specific behaviours. Therefore, general and carbon-specific environmental behaviours are related and may be driven by general attitudes and knowledge (i.e. both carbon-specific and general environmental knowledge). The implications of the study would suggest that marketers, working in tandem with government policymakers, need to focus efforts on developing consumers' knowledge about specific sub-issues, such as global warming. However, additional research needs to be undertaken to develop marketing communication that accurately reflects the environmental impact of consumption behaviour, thereby allowing for considered consumption

The involvement of aβ in the neuroinflammatory response

In the same year as Alzheimer described the case of Auguste D. as a peculiar disease of the cerebral cortex, Fischer published his classic paper about miliary plaque formation in a large number of brains from patients with senile dementia [1]. In this paper and a following one from 1910, Fischer stated that plaque formation is the result of the deposition of a peculiar foreign substance in the cortex that induces a regenerative response of the surrounding nerve fibers [2]. He described spindle-shaped thickening of nerve fibers terminating with club forms in the corona of plaques (Fig. 4.1). These altered nerve fibers were considered as axonal sprouting, and the terminal club forms showed a strong similarity with the clubshaped buddings of axons found in developing nerve fibers and after transections of peripheral nerves as described by Cajal some years earlier. According to Fischer, the crucial step of the plaque formation is the deposition of a foreign substance that provokes a local inflammatory response step followed by a regenerative response of the surrounding nerve fibers. However, Fischer could not find morphological characteristics of an inflammatory process around the plaques after extensive histopathological observations including complement binding studies. The only tissue reaction appeared to be an overgrowth of club-formed neurites