Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q04609 (prostate-specific membrane antigen)
 1,287 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane protein with folate hydrolase and NAALAdase activity. PSMA is highly expressed in prostate cancer and the vasculature of most solid tumors, and is currently the target of a number of diagnostic and therapeutic strategies. PSMA is also expressed in the brain, and is involved in conversion of the major neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glutamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and schizophrenia. To facilitate analysis of the role of PSMA in carcinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 nt portion of the 5' region of the PSMA gene was able to drive the firefly luciferase reporter gene in prostate but not breast-derived cell lines. We have mapped the gene encoding PSMA to 11p11-p12, however a gene homologous, but not identical, to PSMA exists on chromosome 11q14. Analysis of sequence differences between non-coding regions of the two genes suggests duplication and divergence occurred 22 million years ago.
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PMID:Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. 983 72

Glutamate is the predominant excitatory neurotransmitter used by primary afferent synapses and neurons in the spinal cord dorsal horn. Glutamate and glutamate receptors are also located in areas of the brain, spinal cord and periphery that are involved in pain sensation and transmission. Not surprisingly, glutamate receptors have been an attractive target for new pain therapies. However, their widespread distribution and array of function has often resulted in drugs targeting these sites having undesirable side-effects. This chapter will review, in general terms, the current knowledge of glutamate and its effects at various glutamate receptors with regards to nociception. In addition, we will briefly review the glutamatergic drugs currently in use as treatments for pain, as well as known novel candidates in various stages of clinical trial. Lastly, we will summarize the data supporting a novel target for pain intervention by way of GCPII inhibition, which appears devoid of the side-effects associated with direct glutamate receptor antagonists and thus holds major promise for future therapy. GCPII (glutamate carboxypeptidase II) cleaves the prevalent neuropeptide NAAG into NAA and glutamate and there is widespread evidence and belief that targeting the glutamate derived from this enzymatic action may be a promising therapeutic route.
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PMID:The role of glutamate signaling in pain processes and its regulation by GCP II inhibition. 2230 11