Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the immunocytochemical distribution of the prion or proteinase-resistant protein (PrP) during the evolution of experimental Creutzfeldt-Jakob disease (CJD) in mice. Fifty-one brains were collected up to 22 weeks following intracerebral inoculation with the Fujisaki strain of the CJD agent. Slides were also immunostained for apolipoprotein E (apoE) and glial fibrillary acidic protein. Vacuolar changes with focal astrocytosis first occurred around the needle track at week 2 and later spread along white matter tracks. Until week 12, changes were asymmetrical, affecting more the side of inoculation. Spongiform change and astrogliosis spread subsequently to the gray matter. Time course and intensity of spongiform change and immunocytochemistry for PrP were discrepant: in most brain regions, severe vacuolation preceded immunocytochemically detectable PrP accumulation. PrP deposits in form of small dots were first detectable at week 6 in the area surrounding the needle track. After week 7, plaque-like amorphous PrP deposits were observed in white matter pathways. Finally, PrP was detectable also in basal ganglia and in the dorsal hippocampus (week 13) and in the neocortex (week 17), as the synaptic type of PrP immunopositivity. In the hippocampus, diffuse PrP deposits paralleled spongiform change, while in the cortex severe vacuolation was accompanied only by weak synaptic PrP deposits. Immunocytochemically detectable apoE was restricted to compact plaque-type PrP deposits after week 15. We conclude that disease-specific neuropathology spreads from the needle track along white matter pathways towards the gray matter; in this model, there is some discrepancy between development of tissue pathology and immunocytochemically detectable deposition of PrP. Immunocytochemically detectable apoE deposition follows PrP accumulation.
 ...
PMID:Deposition of the prion protein (PrP) during the evolution of experimental Creutzfeldt-Jakob disease. 1060 35

2-aminothiazoles is a class of compounds capable of treating life-threatening prion diseases. QSAR studies on a set of forty-seven 2-aminothiazole derivatives possessing anti-prion activity were performed using multivariate analysis, which comprised of multiple linear regression (MLR), artificial neural network (ANN) and support vector machine (SVM). The results indicated that MLR afforded reasonable performance with a correlation coefficient (r) and root mean squared error (RMSE) of 0.9073 and 0.2977, respectively, as obtained from leave-one-out cross-validation (LOO-CV). More sophisticated learning methods such as SVM provided models with the highest accuracy with r and RMSE of 0.9471 and 0.2264, respectively, while ANN gave reasonable performance with r and RMSE of 0.9023 and 0.3043, respectively, as obtained LOO-CV calculations. Descriptor analysis from the regression coefficients of the MLR model suggested that compounds should be asymmetrical molecule with low propensity to form hydrogen bonds and high frequency of N content at topological distance 02 in order to provide good activities. Insights from QSAR studies is anticipated to be useful in the design of novel derivatives based on the 2-aminothiazole scaffold as potent therapeutic agents against prion diseases.
...
PMID:QSAR study of anti-prion activity of 2-aminothiazoles. 2741 19