Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia

Figure 3

PDE-4/cAMP/CREB cascade in cognition: bidirectional regulation of cyclicAMP (cAMP) homeostasis is achieved through adenylate cyclase (AD) and phosphodiesterase (PDE) subtype 4. cAMP is activated via either PDE-4 inhibition or hormone/neurotransmitter-stimulated adenylate cyclase (AD). The cAMP-dependent protein kinase A (PKA), once activated through allosteric site, can phosphorylate cAMP response element binding protein (CREB) to form phosphorylated CREB: pCREB. pCREB associates with transcription coactivator, CREB binding protein to initiate transcription and translation. The CREB-mediated gene expression contributes towards long- and short-term memory and synaptic plasticity. Zembrin extract modulates PDE-4 and participates in PDe-4/cAMP/CREB cascade in cognition. The CREB-linked gene expression has been shown to be impaired in AD model. ATP: adenosine triphosphate; cAMP: cyclic adenosine monophosphate; adenylate cyclase: AC; 5′AMP: 5′ adenosine monophosphate; CREB: cAMP response element binding protein; pCREB: phosphorylated CERB; PKA: phosphokinase A.