Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ginsenoside, the active principles in Panax ginseng root, has been demonstrated to show neurotrophic and neuroprotective actions for prevention of neuron degeneration. Deposition of beta-amyloid peptide (Abeta) causes neurotoxicity through the formation of plaques in brains with Alzheimer's disease. Pituitary adenylate cyclase-activating polypeptide (PACAP) is introduced as a neurotrophic factor to promote cell survival. However, effect of Rh2, one of ginsenosides, on PACAP expression induced by Abeta remains unclear. In the present study, we found that Rh2 stimulates PACAP gene expression and cell proliferation in type I rat brain astrocytes (RBA1) cells and both effects were not modified by the estrogen antagonists (MPP or ICI 182780). Also, Rh2 ameliorates the RBA1 growth inhibition of Abeta. Moreover, blockade of PACAP receptor PAC1 using PACAP (6-38) inhibits all the actions of Rh2. These results suggest that Rh2 can induce an increase of PACAP to activate PAC1, but not estrogen receptor, and thereby leads to attenuate Abeta-induced toxicity. Thus, ginseng seems useful in the prevention of dementia.
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PMID:Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes. 1831 48

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide that exerts a large array of actions in the central nervous system and periphery. Through the activation of PAC1 and VPAC1, PACAP is able to exert neuroprotective, as well as anti-inflammatory effects, two phenomena involved in the pathogenesis and the progression of neurodegenerative diseases. The aim of the current study was to provide insights into the molecular arrangement of the amino terminus of PACAP and to develop new potent and selective PAC1/VPAC1 agonists promoting neuronal survival. We have synthesized a series of PACAP derivatives and measured their binding affinity and their ability to induce intracellular calcium mobilization for each receptor, i.e. PAC1, VPAC1, and VPAC2. Ultimately, analogs with an improved pharmacological profile were evaluated in an in vitro model of neuronal loss. Results showed that introduction of a hydroxyproline or an alanine moiety, respectively, at position 2 or 7 generated derivatives without significant VPAC2 agonistic activity. Moreover, the structure-activity relationship study suggests the presence of common (Asx-turn like) and distinct (different N-capping type) secondary structures that might be responsible for receptor recognition, selectivity and activation. Finally, evaluation of the neuroprotective activity of [Ala(7)]PACAP27 and [Hyp(2)]PACAP27 demonstrated their ability to protect potently human dopaminergic SH-SY5Y neuroblasts against the toxicity of MPP(+), in pre- and co-treatment experiments. These new pharmacological and structural data should prove useful for the rational design of PACAP-derived compounds that could be putative therapeutic agents for the treatment of neurodegenerative diseases.
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PMID:Design and in vitro characterization of PAC1/VPAC1-selective agonists with potent neuroprotective effects. 2111 61