Skip to main content
. Author manuscript; available in PMC: 2009 Dec 4.
Published in final edited form as: Bipolar Disord. 2009 May;11(3):256–269. doi: 10.1111/j.1399-5618.2009.00675.x

Fig. 1.

Fig. 1

Schematic representation of valproate’s intracellular cytoprotective mechanisms. Fas ligand (FasL)/Fas interactions cause effector caspase activation. FasL-mediated apoptosis can be blocked by the inhibition of caspase-8 protease through cellular Fas-associated death domain-like interleukin- 1-beta-converting enzyme-inhibitory protein (c-FLIP). Valproate (VPA) activates mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and PI- 3K pathways, which upregulate Notch3, c-FLIP, and other proteins (Bcl-2, BDNF, etc.) via transcriptional factors. VPA also regulates gene expression by inhibiting histone deacetylase (HDAC). Hatched lines represent membrane; dotted lines represent indirect effects. FADD = Fas-associated death domain- containing protein.