MicroRNAs and Cellular Phenotypy

This Essay explores the notion that specialized cells have unique vulnerabilities to environmental contingencies that microRNAs help to counteract. Given the ease with which new microRNAs evolve, they may serve as ideal facilitators for the emergence of new cell types

MicroRNAs: regulators of oncogenesis and stemness

MicroRNAs (miRNAs) are essential post-transcriptional regulators that determine cell identity and fate. Aberrant expression of miRNAs can lead to diseases, including cancer. Expression of many miRNAs in the de-differentiated brain tumor cancer stem cells resembles that of neural stem cells. In this issue of BMC Medicine, Silber et al provide evidence of the expression of such miRNAs and their potential to mediate differentiation in both stem cell populations. In this commentary, we discuss the known functions of miRNAs in cancer and stem cells, their therapeutic potential and how the findings of Silber et al provide insight into the role of miR-124/miR-137 dysregulation in glioblastomas

Neurodegeneration: new clues on inclusions

AbstractThe rare neurological disorders frontotemporal dementia and British dementia have been linked to two mutant genes whose products constitute the fibrils that define the two disease pathologies. Two recent studies add to the mounting circumstantial case that protein fibrillization, inside (neurofibrillary tangles) or outside (amyloid plaques) of the neuron, may be pathogenic and suggest that either or both of these mechanisms could initiate Alzheimer’s disease

Structure–activity relationship study of 2,4-diaminothiazoles as Cdk5/p25 kinase inhibitors

Cdk5/p25 has emerged as a principle therapeutic target for numerous acute and chronic neurodegenerative diseases, including Alzheimer’s disease. A structure–activity relationship study of 2,4-diaminothiazole inhibitors revealed that increased Cdk5/p25 inhibitory activity could be accomplished by incorporating pyridines on the 2-amino group and addition of substituents to the 2- or 3-position of the phenyl ketone moiety. Interpretation of the SAR results for many of the analogs was aided through in silico docking with Cdk5/p25 and calculating protein hydrations sites using WaterMap. Finally, improved in vitro mouse microsomal stability was also achieved