A Driver Behind CNS Disease
Howard L. Weiner, MD
A research team led by Oleg Butovsky, PhD, and Howard L. Weiner, MD, BWH Department of Neurology, discovered unique genetic signatures that differentiate specific immune cells responsible for neuroinflammation from other immune cells in the central nervous system (e.g., brain and spinal cord). Furthermore, the expression of these signatures is driven by a gene known as transforming growth factor beta 1 (TGF-beta 1). The findings may one day be applied to clinical scenarios to treat debilitating neurological diseases, such as multiple sclerosis, Lou Gehrig’s disease and Alzheimer’s disease.
In the pre-clinical study, the researchers identified 239 genes and eight microRNAs (molecules that regulate gene expression) that were uniquely or highly expressed in brain immune cells—known as microglia—versus other immune cells that infiltrate the central nervous system. Moreover, TGF-beta 1, which is a protein that helps regulate the life cycle of cells, was needed for in vitro and in vivo development of adult microglia, in both pre-clinical and human models, expressing these unique signatures. The researchers also observed that microglia were absent in the central nervous system of mice without TGF-beta 1, resulting in late onset motor dysfunction. These findings further support previous work demonstrating the protective effects TGF-beta 1 has against various nervous system abnormalities.
“Our studies provide a basic understanding of microglial cells, which now means we can manipulate these cells to treat human disease,” said Weiner.
The study was published online December 8, 2013 in Nature Neuroscience.