High-content analysis methods provide the opportunity to interrogate specific cellular end points in living cells. When coupled with high-throughput RNA interference (ht-RNAi) loss of function screens, high-content analyses are a powerful discovery tool for the identification of new genes and pathways involved in specific disease-relevant cellular functions. The most common readout is a fluorescence measurement, usually based on a green fluorescent protein reporter (or some derivative thereof ) or a fluorescently labeled antibody.
View Article and Find Full Text PDFBackground: Neurofibrillary tangles (NFT), a cardinal neuropathological feature of Alzheimer's disease (AD) that is highly correlated with synaptic loss and dementia severity, appear to be partly attributable to increased phosphorylation of the microtubule stabilizing protein tau at certain AD-related residues. Identifying the kinases involved in the pathologic phosphorylation of tau may provide targets at which to aim new AD-modifying treatments.
Results: We report results from a screen of 572 kinases in the human genome for effects on tau hyperphosphorylation using a loss of function, high-throughput RNAi approach.
Technology for high-throughout scanning of the human genome and its encoded proteins have rapidly developed to allow systematic analyses of human disease. Application of these technologies is becoming an increasingly effective approach for identifying the biological basis of genetically complex neurological diseases. This review will highlight significant findings resulting from the use of a multitude of genomic and proteomic technologies toward biomarker discovery in neurological disorders.
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