Massive elimination of neurons is a critical aspect of normal nervous system development, but also represents a defining feature of neurodegenerative pathologies, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis(ALS or Lou Gehrig’s disease). Although the molecular events that trigger neuronal death in each of these neurodegenerative diseases are distinct, the downstream apoptotic process through which neurons die in these pathologies are thought to share commonalities to each other, as well as to developmentally-regulated neuronal death. Identifying genes that promote or prevent neuronal death would thus be an important step in understanding both developmentally-regulated neuronal death as well as the mechanisms underlying degenerative brain disorders. Scientists at Southern Methodist University (SMU), led by Professor and Chair of Biological Sciences Dr. Santosh D'Mello, have used RNA-Seq to conduct transcriptome profiling of gene expression changes in dying neurons. This study, reported [online] in the February 2015 issue of Experimental Biology and Medicine, utilized cultured cerebellar granule neurons, one of the most widely used models to study neuronal death. Other labs have used DNA microarray analysis to characterize gene expression changes in this model. However, microarray analysis is only capable of measuring the status of known transcripts, and expression of low-abundance mRNAs is often not detected by the hybridization-based approach. While changes in the expression of several hundred genes were detected by microarray analyses, in the study by Dr. D'Mello and colleagues, over 4,000 genes displayed significantly altered expression. Most affected were genes functioning in cell death and survival regulation, cell growth and proliferation, and molecular transport.
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