86,792 research outputs found
Protein kinase C isoforms as therapeutic targets in nervous system disease states
No full textNeuronal tissues display high levels of protein kinase C (PKC) activity and isoform expression. The activation of this enzymatic system is important in the control of short and long term brain functions (ion channel regulation, receptor modulation, neurotransmitter release, synaptic potentiation/depression, neuronal survival) that are related to diverse brain pathologies. This review will describe recent developments in PKC regulation and changes in levels, isoforms and activation in acute and chronic neurodegenerative pathologies as well as in affective and psychic disorders. The recent availability of isoform selective inhibitors and activators may help to understand better the relevance of PKC in central nervous system (CNS) physiology and pathology and to identify new and safer pharmacologic strategies to be tested in different disease states. © 2001 Academic Press
Ranking and classification of non-ionic organic pesticides for environmental distribution: A QSAR approach
No full textProtein Kinase C Signal Transduction Regulation in Physiological and Pathological Aging
No full textCalcium/phospholipid-regulated protein kinase C (PKC) signalling
is known to be involved in cellular functions relevant to brain health and disease, including ion channel modulation, receptor regulation, neurotransmitter
release, synaptic plasticity, and survival. Brain aging is characterized by altered neuronal molecular cascades and interneuronal communication in response to various stimuli. In the last few years we have provided evidence
that in rodents, despite no changes in PKC isoform levels (both calcium dependent and calcium independent), the activation/translocation process of the calcium-
dependent and -independent kinases and the content of the adaptor protein RACK1 (receptor for activated C kinase-1) are deficient in physiological brain aging. Moreover, human studies have shown that PKC and its adaptor protein RACK1 are also interdependent in pathological brain aging (e.g.,
Alzheimer’s disease); in fact, calcium-dependent PKC translocation and RACK1 levels are both deficient in an area-selective manner. These data point
to the notion that, in addition to a well-described lipid environment alteration, changes in protein–protein interactions may impair the mechanisms of PKC
activation in aging. It is interesting to note that interventions to counteract the age-related functional loss also restore PKC activation and the adaptor protein
machinery expression. A better insight into the factors controlling PKC activation may be important not only to elucidate the molecular basis of signal transmission,
but also to identify new strategies to correct or even to prevent agedependent alterations in cell-to-cell communication
Ranking of aquatic toxicity of esters modelled by QSAR
No full textAlternative methods like predictions based on Quantitative Structure–Activity Relationships (QSARs) are now accepted to fill data gaps and define priority lists for more expensive and time consuming assessments. A heterogeneous data set of 74 esters was studied for their aquatic toxicity, and available experimental toxicity data on algae, Daphnia
and fish were used to develop statistically validated QSAR models, obtained using multiple linear regression (MLR) by the OLS (Ordinary Least Squares) method and GA-VSS (Variable Subset Selection by Genetic Algorithms) to predict missing values. An ESter Aquatic Toxicity INdex (ESATIN) was then obtained by combining, by PCA, experimental and predicted toxicity data, from which model outliers and esters highly influential due to their structure had been eliminated.
Finally this integrated aquatic toxicity index, defined by the PC1 score, was modelled using only a few theoretical molecular descriptors. This last QSAR model, statistically validated for its predictive power, could be proposed as a preliminary evaluative method for screening/prioritising esters according to their integrated aquatic toxicity, just starting from their molecular structure
Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drug.
No full textHappy birthday protein kinase C: Past, present and future of a superfamily
No full text[No abstract available
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