MicroRNA Blocks Proapoptotic Genes in Mature Nerve Cells

A microRNA (miRNA) has been identified that blocks the activity of proapoptotic proteins in mature nerve cells and may be a potential drug for the treatment of neurodegenerative disorders.

During development, nerve cells that fail to connect to target tissues self-destruct. Yet, once such connections are made, surviving neurons become resistant to apoptosis for the life span of the organism.

Investigators at the University of North Carolina (Chapel Hill, USA) studied the mechanism underlying this radical change in behavior. They considered the class of gene-regulating molecules known as microRNAs to be a particularly promising target. To this end, they screened all known miRNAs to identify differences between immature and mature neurons.

Results published in the January 15, 2011, online edition of the journal Genes & Development revealed that the microRNA miR-29 was markedly induced with neuronal maturation. Immature neurons that would normally die became resistant to apoptosis following exposure to miR-29. Furthermore, analysis of brain tissues from patients with Alzheimer's disease or Huntington's disease showed reduced levels of miR-29.

The investigators reported that at the molecular level miR-29 blocked the activity of the genes that encode the BH3-only proapoptotic protein family. MiR-29 was able to inhibit several of these genes, circumventing a redundancy that allowed apoptosis to continue even if one of them had been blocked.

"There is the real possibility that this molecule could be used to block the cascade of events known as apoptosis that eventually causes brain cells to break down and die,” said senior author Dr. Mohanish Deshmukh, associate professor of cell and developmental biology at the University of North Carolina.

"People in the field have been perplexed that when they have knocked-out any one of these members it has not had a remarkable effect on apoptosis because there are others that can step in and do the job,” said Dr. Deshmukh. "The fact that this microRNA can target multiple members of this family is very interesting because it shows how a single molecule can basically in one stroke keep apoptosis from happening. Interestingly, it only targets the members that are important for neuronal apoptosis, so it may be a way of specifically preserving cells in the brain without allowing them to grow out of control (and cause cancer) elsewhere in the body.”

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