Schizophrenia genetics and its complexities are beginning to yield to large genome-wide studies. One of the recently identified top risk loci, miR 137, can be seen as a master key that unlocks other doors. The Mir 137 locus encodes a micro RNA that regulated hundreds of other genes, and several of those are also linked to schizophrenia.
Earlier this month, Emory’s chair of cell biology Gary Bassell and former graduate student Kristen Thomas published a paper in Cell Reports analyzing how perturbing Mir 137 affects signaling in neurons. Inhibiting Mir 137 blocked neurons’ responses to neuregulin and BDNF, well-known growth factors.
“We think a particularly interesting aspect of our paper is that it links miR137, neuregulin and ErbB4 receptor: three molecules with known genetic risk for schizophrenia,” Bassell writes.
He and Thomas make the case that nudging miR 137 up or down can both be harmful.
“If miR137 is too high or low, it will affect levels of its targets in the PI3K mTOR pathway,” Bassell writes. “If the components are elevated, the pathway is saturated and insensitive to neuregulin. If the components are too low, they’re insufficient to be activated.”
This research may not lead to new treatments immediately. But in this situation, just understanding better what’s happening to brain development in schizophrenia and how the many genetic risk factors exert their effects is valuable. The same can be said for other recent advances in understanding schizophrenia.