Manganese is an essential mineral that at high concentration acts as a neurotoxin which produces a Parkinson-like syndrome. Current studies are focused on characterizing the signal transduction pathways stimulated by manganese and to determine whether they also play a role in the toxic actions of this divalent cation. In addition, we are currently examining the mechanism by which the pineal hormone, melatonin, can inhibit the cell cycle and suppress cell death in PC12 cells. Preliminary studies suggest the antiproliferative effects of melatonin may be mediated via its cell surface receptor and studies are currently underway to determine which of the cell cycle genes are regulated by this hormone. Since melatonin has been proposed to be an anti-aging agent, the mechanism of suppression of PC12 cell death is also being investigated.
Studies are also underway to understand the mechanism by which melatonin stimulates bone growth.
Representative Publications Roth, J. A., Rabin, R. and Agnello, K. Melatonin Suppression of PC 12 Cell Growth and Death. Larsen, K.E., Pacheco, M. Roth, J.A. and Aletta, J.M. Increased MAP1B Expression without Increased Phosphorylation in Manganese-Treated PC12Mn Cells. Gallagher, P.J., Amodeo, J.L., Howie, H, Roth J.A., and Lein, P.J., Manganese induces neurite outgrowth in PC12 cells via upregulation and activation of alpha V Integrins.