Modes of Action of Taurine and Granulocyte Colony-stimulating Factor in Neuroprotection

Summary schematic depicting the mode of action of taurine in neuroprotection. The sequence of events leading from the activation of taurine receptors to neuroprotection can be summarized as follows: (1) activation of ionotropic taurine receptors (iTauR) and/or activation of metabotropic taurine receptors (mTauR); (2) inhibition of the reverse mode of sodium/calcium exchangers; (3) inhibition of voltage-gated calcium channels (VGCC) by taurine-induced hyperpolarization; (4) inhibition of calpain resulting from the decrease in the intracellular free-calcium concentration; (5) inhibition of the cleavage of Bcl-2 and Bax by the inhibition of calpain; (6) inhibition of the formation of the Bax homodimer, leading to the inhibition of apoptosis; (7) activation of mTauR, which is negatively coupled to inhibitory G proteins, resulting in the inhibition of phospholipase C (PLC) activity and a decrease in IP3 production; (8) decreased IP3 level inhibits the release of calcium from the internal calcium storage pools, such as the ER, resulting in reduced ER stress and inhibition of apoptosis.

Proposed mode of action of the neuroprotective functions of G-CSF. G-CSF could exert its neuroprotective functions through one or more of the following signaling pathways: (1) activation of the STAT3 pathway results in translocation of STAT3 to the nucleus and (2) the upregulation of the anti-apoptotic genes, Bcl-2 and Bcl-X; (3) activation of the PI3K/AKT pathways or (4) ERK1/2 pathway results in the inhibition of the pro-apoptotic protein, Bad; (5) activation of the PI3K/AKT pathways inhibits the ER stress-mediated ASK-1 pathway, resulting in disinhibition or activation of the anti-apoptotic protein, Bcl-2, and inactivation of the pro-apoptotic protein, BIM (see insert).