Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebrospinal fluid (CSF) and serum or plasma concentrations of albumin, IgG and carbidopa were measured before and after adrenal-brain transplantation in patients with Parkinson's disease to indirectly assess blood-brain barrier (BBB) integrity. Previous studies in animals have suggested that the BBB is compromised by cerebral transplantation. CSF and plasma levodopa was also measured to permit comparison with the carbidopa values, recognizing that levodopa readily crosses the BBB via facilitated transport. Our patients underwent adrenal-brain transplantation in accordance with the method of Madrazo et al. (I. Madrazo, R. Drucker-Colin, V. Diaz, J. Martinez-Mata, C. Torres, and J. J. Becerril, 1987, N. Engl. J. Med. 316: 831-834) in which adrenal medullary pieces are implanted in the head of the caudate nucleus, in contact with the cerebrospinal fluid. All patients were maintained on oral carbidopa/levodopa therapy after surgery. CSF albumin/serum albumin and CSF IgG/serum IgG ratios were initially elevated above the preoperative baseline 6 weeks after the surgery; however, these values returned to the preoperative baseline by 6 months following the operation in six of seven patients. This suggested that the BBB was sufficiently intact to exclude these larger protein molecules from the CSF of these six patients. On the other hand, exogenously administered carbidopa, which normally is largely excluded from the cerebrospinal fluid by the BBB, was modestly increased in the CSF in four of the five patients in which it was measured. This suggests that the transplant BBB might be partially patent to small molecules for at least 6 months after the surgery. Whether increased passage of carbidopa into CSF and perhaps the transplant is of clinical significance has yet to be determined. Median CSF levodopa did not increase after surgery, probably because a limited defect in the BBB would be likely to be overshadowed by the effects of facilitated transport. CT scans performed following intravenous iothalamate meglumine contrast failed to reveal enhancement (dye leakage) near the transplantation site; however, artifact from the metal surgical clips used in the Madrazo procedure prevented good visualization of the area.
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PMID:Cerebrospinal fluid indices of blood-brain barrier permeability following adrenal-brain transplantation in patients with Parkinson's disease. 275 15

This special issue is based on a mini-symposium in the area of neurosciences with the title "Understanding the role of heteroreceptor complexes in the central nervous system" held at the Nobel Forum, Karolinska Institutet on December 17th, 2012, organized by Kjell Fuxe, Dasiel O. Borroto-Escuela and Luigi F. Agnati. It consists of seven mini-reviews in the field receptor heteromers. The early work on negative cooperativity and neuropeptide-monoamine receptor-receptor interactions in the central nervous system gave the first indications of the existence of homomers and heteromers of G-protein coupled receptors (GPCR), respectively, and the GPCR field began to expand from monomers into dimers and receptor mosaics (higher-order dimers). It was underlined that the existence of receptor heteromers with allosteric receptor-receptor interactions increases the diversity and bias of GPCR recognition and signalling. The molecular phenomenon of allosteric receptor-receptor interactions is proposed to give a better understanding of brain function through molecular integration of signals. An alteration in specific receptor-receptor interactions is in fact considered to play a role in pathogenic mechanisms leading to several diseases, inter alia Parkinson's disease, hypertension, schizophrenia, addiction and depression. It is a new principle in molecular medicine. Therefore, pharmacological targeting of receptor-receptor interactions in heteromers will become an important area for developing more selective drugs with reduced side-effects including heterobivalent compounds and optimal types of combined treatments. In other words , it will lead to novel strategies for treatment, and finally novel drugs for treatment of disease. The first mini-review by Dr. Tena-Campus and colleagues introduces the field of GPCR oligomerization as emerging signalling units with new opportunities for drug design and discusses the technologies involved for detection of receptor heteromers. Then the issue moves into examples of receptor-receptor interactions in the DA and neuropeptide field. Dr. Van Craenenbroeck and colleagues presents an article on the role of dimerization in the biogenesis of DA D4 receptors and thus in their maturation. Dr. Zaida Diaz-Cabiale and colleagues describe the existence of galanin receptor-neuropeptide Y receptor interactions in the brain including galanin receptor-neuropeptide Y Y1 interactions in the brain stem. Indications are obtained that the receptor target for galanin fragment 1-15 is instead a GalR1-GalR2 heteromer. Then the special issue enters into the role of receptor-receptor interactions in putative striatal GPCR heteromers in Parkinson's disease and schizophrenia. Dr. Beggiato and colleagues discuss the role of antagonistic adenosine A2A-D2 receptorreceptor interactions in the striato-pallidal GABA neurons and their relevance for treatment of Parkinson's disease. They give the rationale for the introduction of A2A receptor antagonists in clinical trials in this disease based on these antagonistic receptor- receptor interactions which become even more strongly developed in animal models of Parkinson's disease. Dr. Luca Ferraro and colleagues instead discuss in detail the antagonistic Neurotensin NTS1-dopamine D2 receptor-receptor interactions in putative receptor heteromers in the dorsal and ventral striatum. Their involvement in striato-pallidal GABA and mesocorticolimbic DA communication is discussed with focus on their relevance for Parkinson's disease, schizophrenia and their treatments. Dr. Di Liberto and colleagues deal with the role of receptor-receptor interactions in brain trophism and plasticity with focus on interactions between G protein-coupled receptor-Receptor Tyrosine Kinase, specially the cholinergic and fibroblast growth factor receptor 1 (FGFR1). mAChR-FGFR1 interactions are indicated leading to transactivation of FGFR1 with potential relevance for cognition. Luigi Agnati and colleagues in the last paper of this special issue suggest a unified perspective for integrative brain actions through " neurosemeiotics" and " free energy minimization". Especially the Bio-semeiotics concept of "adaptor" may involve the receptor-receptor interactions in heteroreceptor complexes. Through such "adaptors" a code may be produced that give meaning to the sensory stimuli reaching the cortical regions of the brain . We hope the readers will find the articles in this special issue of interest and may give some inspiration to enter this exciting field of receptor research in the CNS which opens up a novel understanding of the molecular events that may lead to neurological and mental diseases and offer novel strategies for their treatments. The editors are grateful to the authors for their fine contributions to this special issue.
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PMID:Understanding the role of heteroreceptor complexes in the central nervous system. 2525 22