Figure 1.

Schematic presentation of proposed mechanisms by which GTPP and other natural products counteract Nogo-A and other axonal growth inhibitors.

Binding of Nogo-A and other axonal growth inhibitors to NgR1 receptor complex leads to activation of RhoA and its effector, RhoA-associated protein kinase (ROCK). This ultimately leads to reorganization of actin cytoskeleon, causing growth cone collapse and neurite outgrowth inhibition. EGCG binding to its cell-surface receptor leads to activation of NADPH oxidase and an increase in the generation of H₂O₂ (Gundimeda et al., 2012). Either endogenously generated H₂O₂ in response to EGCG treatment or exogenous H₂O₂ alone prevents the antineuritogenic action of Nogo-A (Gundimeda et al., 2015). We hypothesize that H₂O₂ may accomplish this directly through inhibiting RhoA by either inducing its redox modification or enhancing tyrosine phosphorylation-mediated activation of p190RhoGAP, an endogenous inhibitor of RhoA. Various natural products from Chinese medicines may decrease the expression of Nogo-A and/or NgR1 and enhance axonal regeneration (Qin et al., 2012). Daidzein, a soy isoflavone, blocks the antineuritogenic action of MAG by inducing arginase and polyamine synthesis (Ma et al., 2010). 67LR: 67-kDa laminin receptor; EGCG: epigallocatechin-3-gallate; GTPP: green tea polyphenols; MAG: myelin-associated glycoprotein; NADPH: nicotinamide adenine dinucleotide phosphate; NgR1: Nogo-66 receptor 1; OMgp: oligodendrocyte myelin glycoprotein.