N-acetylaspartylglutamate (NAAG) and Glutamate Carboxypeptidase II: An abundant peptide neurotransmitter-enzyme system with multiple clinical applications

Publication date: Available online 12 November 2019Source: Progress in NeurobiologyAuthor(s): Joseph H. Neale, Tatsuo YamamotoAbstractN-Acetylaspartylglutamate (NAAG) is the third most prevalent neurotransmitter in the mammalian nervous system, yet its therapeutic potential is only now being fully recognized. Drugs that inhibit the inactivation of NAAG by glutamate carboxypeptidase II (GCPII) increase its extracellular concentration and its activation of its receptor, mGluR3. These drugs warrant attention, as they are effective in animal models of several clinical disorders including stroke, traumatic brain injury and schizophrenia. In inflammatory and neuropathic pain studies, GCPII inhibitors moderated both the primary and secondary pain responses when given systemically, locally or in brain regions associated with the pain perception pathway. The finding that GCPII inhibition also moderated the motor and cognitive effects of ethanol intoxication led to the discovery of their procognitive efficacy in long-term memory tests in control mice and in short-term memory in a mouse model of Alzheimer’s disease. NAAG and GCPII inhibitors respectively reduce cocaine self-administration and the rewarding effects of a synthetic stimulant. Most recently, GCPII inhibition also has been reported to be efficacious in a model of inflammatory bowel disease. GCPII was first discovered as a protein expressed by and released from metastatic prostate cells where it is known as prostate spe...
Source: Progress in Neurobiology - Category: Neuroscience Source Type: research

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This study investigated the protein expression profile of STC1 in PCa and benign prostatic hyperplasia (BPH) samples and STC1 signalling during cell proliferation and cell death in vitro using cell lines. We found higher levels of STC1 in PCa when compared to BPH tissue and that STC1 inhibited forskolin stimulation of cAMP in PC-3 cells. A monoclonal antibody against STC1 was effective in reducing cell proliferation, in promoting cell cycle arrest, and in increasing apoptosis in the same cells. Since STC1 acts as a regulator of prostatic tissue signalling, we suggest that this protein is a novel candidate biomarker for p...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
Authors: Lee YH, Jang HW, Park CH, An SM, Lee EK, Choi BM, Noh GJ Abstract BACKGROUND: The aim of intraoperative fluid therapy is to avoid both hypovolemia and hypervolemia; however, the patient's exact volume status is difficult to determine during surgery. Fluid optimization guided by stroke volume variation (SVV) has been widely used in patients undergoing major open abdominal surgery. The aim of this study was to evaluate the changes in plasma volume before and after surgery following SVV-guided fluid therapy. METHODS: Patients were randomly allocated into one of two groups according to the SVV criteria for...
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
CONCLUSIONS: CNB and SSNB have similar effects on pain relief, complications and functional recovery in patients receiving TKA. The optimal analgesic regimen for patients after TKA needs further identification. PMID: 31808660 [PubMed - as supplied by publisher]
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
Publication date: Available online 6 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Lorenzo GalluzziAlthough somatic KRAS mutations are common in human tumors, no inhibitor of mutant KRAS was clinically available until recently. Canon and colleagues describe the ability of a clinically available KRASG12C inhibitor to drive immunogenic cancer cell death, thus constituting a promising combinatorial partner for immune checkpoint blockers.
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 7 December 2019Source: Saudi Pharmaceutical JournalAuthor(s): Kinga OstrowskaAbstractA number of psychiatric disorders, including anxiety, schizophrenia, Parkinson’s disease, depression and others CNS diseases are known to induce defects in the function of neural pathways sustained by the neurotransmitters, like dopamine and serotonin. N-arylpiperazine moiety is important for CNS-activity, particularly for serotonergic and dopaminergic activity. In the scientific literature there are many examples of coumarin-piperazine derivatives, particularly with arylpiperazines linked to a coum...
Source: Saudi Pharmaceutical Journal - Category: Drugs & Pharmacology Source Type: research
ConclusionABCB1 C3435T and ABCG2 C421A might represent a potential risk factor for breast cancer for Turkish women.
Source: Saudi Pharmaceutical Journal - Category: Drugs & Pharmacology Source Type: research
ConclusionThe findings suggest that chitosan, as a prime drug-delivery carrier, significantly alleviates the acute and sub-acute toxic effects of 6-MP.
Source: Saudi Pharmaceutical Journal - Category: Drugs & Pharmacology Source Type: research
ConclusionResults of this study demonstrated the potential of MWL oil in the development of natural anticancer therapeutic agents.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 6 December 2019Source: International Journal of PharmaceuticsAuthor(s): Iftikhar Khan, Maria Apostolou, Ruba Bnyan, Chahinez Houacine, Abdelbary Elhissi, Sakib S YousafAbstractA simplistic approach was conducted to manufacture novel paclitaxel (PTX) loaded protransfersome tablet formulations for pulmonary drug delivery. Large surface area presented by pulmonary system offer better target using anti-cancer drug deposition for localized effect in the lungs. Protransfersomes are dry powder formulations, whereas transfersomes are liquid dispersions containing vesicles generated from protransf...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
Conclusion: These results conclude that G.A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-metastatic effects.Graphical abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
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