Low-molecular-weight compounds having neurotrophic activity in cultured PC12 cells and neurons.

Recent reports have indicated that some low-molecular-weight compounds mimic neurotrophic factors inducing neurite outgrowth and neuroprotection. Carnosic acid (CA) promotes neurite outgrowth through the activation of Nrf2 in PC12 cells. CA also protects neurons via the keap/Nrf2 transcriptional pathway from oxidative stress. Forskolin-induced neurite outgrowth is mediated by activation of the PKA signalling pathway and this PKA-mediated neurite outgrowth is achieved by the expression of nur77 in PC12 cells. In addition, forskolin at its low concentration is closely related to the cAMP-induced protective function against L-DOPA-induced cytotoxicity in PC12 cells. A HDAC inhibitor trichostatin A (TSA) increases neurite length via p53 acetylation in rat cultured cerebellar granule neurons and in cerebral cortical neurons, and also protects neurons against glutathione depletion-induced oxidative stress. Recently, it was revealed that Nrf2 and p53 bind to CBP/p300 directly, and Nur77 is acetylated in vivo and in vitro by CBP/p300. Acetylation of Nrf2, p53 and Nur77 by CBP/p300 may constitute a novel similar regulatory mechanism for low-molecular-weight compounds with neurotrophic activities.