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)

Fifteen patients with Parkinson's disease underwent open transplantation of autologous adrenal medulla to the caudate nucleus. Motor function was evaluated before and after surgery and was found to be significantly improved at 5-9 months following surgery. Cerebrospinal fluid was taken from the ventricle adjacent to the implant site at the beginning of the operation and at 1 week, 3 months, and 5-9 months following surgery. The cerebrospinal fluid was assayed for chromogranin A (CgA), the major soluble protein in chromaffin granules, and basic fibroblast growth factor (bFGF), a neurotrophic growth factor found in normal brain and adrenal medulla. CgA levels did not increase following surgery, suggesting that a significant number of chromaffin cells did not survive or that surviving chromaffin cells did not secrete a significant amount of CgA. Basic fibroblast growth factor was undetectable in the ventricular cerebrospinal fluid.
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PMID:Clinical improvement in parkinsonian patients undergoing adrenal to caudate transplantation is not reflected by chromogranin A or basic fibroblast growth factor in ventricular fluid. 199 31

Studies have suggested that the restorative effects of adrenal medullary chromaffin cell grafts in animal models of Parkinson's disease may be related to trophic factors contained within the chromaffin cells. Basic fibroblast growth factor (bFGF) is present in chromaffin cells and has been shown to exert trophic effects on dopaminergic neurons in vitro. Basic FGF was stereotaxically injected into the striatum of young (2-month-old) and aging (12-month-old) C57BL/6 mice which had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1 week earlier. MPTP treatment reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and striatal dopamine (DA) concentration in both the young and older mice 5 weeks later. Computerized image analysis of striatal DA fibers in young mice treated with bFGF showed significant recovery of DA fibers up to 600 microns from the injection site 5 weeks after MPTP administration. Striatal DA fibers in older mice treated with bFGF showed significant recovery only up to 300 microns from the injection site, and the degree of recovery was very limited compared with young mice. HPLC analysis of DA concentration revealed that striatal DA in young mice recovered significantly when treated with bFGF, but no significant recovery was observed in older mice. It is concluded that bFGF enhances the recovery of striatal DA systems from MPTP toxicity both in young and in older mice, but that such benefits are very limited in older mice.
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PMID:Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging. 810 13

Basic fibroblast growth factor (bFGF) has a neurotrophic effect on mesencephalic dopaminergic neurons in vitro and in vivo. To explore whether an abnormality in bFGF expression occurs in Parkinson's disease (PD), we examined the substantia nigra (SN) of six PD and eight control cases immunohistochemically using a monoclonal antibody to bFGF. The mean number of melanin-positive neurons in sections of PD SN was 30.3% of the control mean, but the number of bFGF-immunopositive neurons was only 4.7% of the control mean. bFGF-immunoreactivity was present in only 8.2% of PD, but in 93.7% of control melanin-positive neurons. These results suggest a profound depletion of bFGF in surviving dopaminergic neurons of the SN in PD, and this depletion may be related to the disease process.
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PMID:Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson's disease. 843 5

Basic fibroblast growth factor (bFGF; FGF-2) has potent trophic effects on developing and toxically impaired midbrain dopaminergic (DAergic) neurons which are crucially affected in Parkinson's disease. The trophic effects of FGF-2 are largely indirect, both in vitro and in vivo, and possibly involve intermediate actions of astrocytes and other glial cells. To further investigate the cellular and molecular mechanisms underlying the restorative actions of FGF-2, and to analyse in more detail the changes within astroglial cells in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-lesioned striatum, we have studied striatal expression and regulation of connexin-43 (cx43), the principal gap junction protein of astroglial cells, along with the expression of glial fibrillary acidic protein (GFAP), FGF-2, and functional coupling. Our results show an immediate, yet transient increase in cx43 mRNA, and a sustained increase in FGF-2 mRNA, GFAP-positive cells, and cx43-immunoreactive punctata following the MPTP lesion, without any induction of functional coupling between astrocytes and other glial cells as revealed by dye coupling of patched cells. Unilateral administration of FGF-2 in a piece of gelfoam caused a further increase in cx43-positive punctata immediately adjacent to the implant, which was more pronounced than after application of a gelfoam containing the nontrophic control protein cytochrome C. These changes were parallelled by a small increase in cx43 protein determined by Western blot, but not by alterations in the coupling state of cells in the vicinity of the gelfoam implant. Although our data indicate that MPTP and exogenous FGF-2 may alter expression and protein levels of cx43, they do not support the notion that increases in cellular coupling may underly the trophic and widespread actions of FGF-2 in the MPTP-model of Parkinson's disease.
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PMID:Regulation of connexin-43, GFAP, and FGF-2 is not accompanied by changes in astroglial coupling in MPTP-lesioned, FGF-2-treated parkinsonian mice. 895 72

The use of neurotrophic growth factors as a means of preventing loss of the dopaminergic (DA) neurons in the substantia nigra (SN) is becoming an accepted treatment strategy for Parkinson's disease (PD). In earlier studies, we showed that there was a selective loss of basic fibroblast growth factor (bFGF) immunoreactivity in DA neurons of the SN in PD suggesting that a deficiency of bFGF might contribute to cell death. As a preliminary step to assessing the potential for using bFGF or its analogs as therapeutic agents, the expression of fibroblast growth factor receptor-1 (FGFR-1) in the SN of normal and PD cases was investigated immunohistochemically. FGFR-1 immunoreactivity could be detected in DA neurons of the SN in young and old neurologically normal cases with an apparent decline with age. FGFR-1 immunoreactivity was also detected in many of the residual SN neurons in most of the idiopathic PD cases. These results indicate that FGFR-1 immunoreactivity, and possibly FGF binding activity, is retained in DA neurons in PD.
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PMID:Immunohistochemical analyses of fibroblast growth factor receptor-1 in the human substantia nigra. Comparison between normal and Parkinson's disease cases. 962 24

Basic fibroblast growth factor is expressed in different isoforms which display tissue and species specificity and are differentially regulated during development and after experimental interventions. The differential regulation of the fibroblast growth factor-2 isoforms may indicate specific activities and functions of these molecules. The characterization of fibroblast growth factor-2 effects, however, is almost exclusively based on studies including the 18,000 mol. wt isoform. It is not yet known whether the high molecular weight fibroblast growth factor-2 isoforms (21,000 mol. wt, 23,000 mol. wt) exert similar or distinct activities in the nervous system. In the present study, we investigated the effects of the high molecular weight isoforms on dissociated rat mesencephalic dopaminergic neurons. For this purpose, recombinant fibroblast growth factor-2 isoforms, prepared in a histidine expression system, were administered on dopaminergic neurons in vitro, and Schwann cells over-expressing the high molecular weight isoforms were co-cultured with dopaminergic neurons. This is the first demonstration to show that the high molecular weight isoforms mediate a neurotrophic activity. Exogenous high molecular weight fibroblast growth factor-2 isoforms stimulated the survival of embryonic mesencephalic dopaminergic neurons and protected them from 6-hydroxydopamine neurotoxicity. In addition, co-culture of dopaminergic neurons with high molecular weight fibroblast growth factor-2 over-expressing Schwann cells revealed an increased survival and neurite formation of the mesencephalic dopaminergic neurons. These results suggest that the high molecular weight fibroblast growth factor-2 isoforms may serve as a new tool for the treatment of Parkinson's disease.
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PMID:The high molecular weight fibroblast growth factor-2 isoforms (21,000 mol. wt and 23,000 mol. wt) mediate neurotrophic activity on rat embryonic mesencephalic dopaminergic neurons in vitro. 1099 60

Basic fibroblast growth factor (bFGF), initially identified as mitogens with prominent angiogenic properties, is now recognized as multifunctional growth factors with notable actions on neuronal cells. bFGF promotes the survival and neurite growth of brain neurons in vitro and in vivo, suggesting that it functions as a neurotrophic factor. This effect of bFGF could be beneficial for improving the survival of grafted neurons in transplantation. Furthermore, bFGF acutely modulates synaptic transmission in the hippocampus, suggesting that it has a role like a neurotransmitter or neuromodulator. In this article, we make a brief review of multiple biological activities of bFGF for brain neurons and discuss its potential usefulness for the treatment of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease.
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PMID:Effects of basic fibroblast growth factor on central nervous system functions. 1135 34

Stem cells are currently considered as alternative cell resources for restorative transplantation strategies in Parkinson's disease. However, the mechanisms that induce differentiation of a stem cell toward the dopaminergic phenotype are still partly unknown thus hampering the production of dopaminergic neurons from stem cells. In the past, FGF-20 has been found to promote the survival of ventral mesencephalic (VM) dopaminergic (DA) neurons in culture. We hereby provide evidence that FGF-20, a growth factor of the FGF family, is expressed in the adult and 6-OHDA-lesioned striatum and substantia nigra, but is not expressed by VM glia or DA neurons, suggesting that FGF-20 may work on DA neurons in a paracrine- or target-derived manner. We also found that co-culture of Nurr1-NSCs with Schwann cells overexpressing FGF-20 induced the acquisition of a neuronal morphology by the NSCs and the expression of tyrosine hydroxylase (TH) as assessed by immunocytochemistry, cell ELISA, and Western blot analysis. RT-PCR showed, that both, Schwann cells and Nurr1-NSCs (differentiated or not), expressed the FGF-1 receptor suggesting that both direct and indirect actions of FGF-20 are possible. We show that differentiated Nurr1 cells retained both neuronal morphology and TH expression after transplantation into the striatum of 6-OHDA-lesioned postnatal or adult rats, but that neuritogenesis was only observed after postnatal grafts. Thus, our results suggest that FGF-20 promotes the differentiation of Nurr1-NSCs into TH-positive neurons and that additional factors are required for the efficient differentiation of DA neurons in the adult brain.
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PMID:Fibroblast growth factor-20 promotes the differentiation of Nurr1-overexpressing neural stem cells into tyrosine hydroxylase-positive neurons. 1547 54

We cloned and characterized human FGF20 in August, 2000. Ohmachi et al claimed the same gene as a novel FGF family member in October, 2000, and Jeffers et al in April, 2001. FGF20 is up-regulated in colorectal cancer due to the activation of WNT/beta-catenin pathway. FGF20 is applicable as the mucosal protective agent for inflammatory bowel disease and chemotherapy/radiation-induced oral mucositis, and also as the inducer of dopaminergic neurons for Parkinson's disease. FGF20 is a target of pharmacogenomics in the field of oncology and regenerative medicine. Here, comparative genomics analyses on FGF20 orthologs were performed. Zebrafish fgf20 gene, consisting of three exons, was located within BX323810.8 genome sequence. Zebrafish fgf20 (208 aa) showed 76.9%, 76.4%, 76.0% and 75.5% total-amino-acid identity with human FGF20, Xenopus fgf20, rat Fgf20 and mouse Fgf20, respectively. Fgf20 orthologs were well conserved among vertebrates. Human FGF20 gene was linked to EFHA2 gene in head-to-head manner with an interval of about 25 kb. FGF20-EFHA2 locus at human chromosome 8p22 and FGF9-EFHA1 locus at human chromosome 13q12.11 were paralogous regions (paralogons) within the human genome. The 5'-flanking promoter region, exonic regions except 3'-UTR, and middle regions within intron 1 were conserved between human FGF20 and mouse Fgf20 genes. Double TCF/LEF binding sites, double EVI1-binding sites, TGIF, PAX4, E47 and AREB6-binding sites were conserved between human FGF20 promoter and mouse Fgf20 promoter.
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PMID:Comparative genomics on FGF20 orthologs. 1594 4

The effects of HSV-1 amplicon and polyethyleneimine (PEI)-mediated transfection of dominant negative FGF receptor-1 mutant FGFR1(TK-) into the rat brain substantia nigra (SN) were examined in vivo to model the reduced FGF signaling documented to occur in Parkinson's disease. The number of SN neurons that expressed tyrosine hydroxylase (TH) was significantly reduced following HSV-1 FGFR1(TK-) intranigral delivery and similar changes were observed after PEI-mediated FGFR1(TK-) transfections. Further, we also observed a significantly lower striatal dopamine content following the PEI transfection of FGFR1(TK-). Thus, we conclude that reduced FGF signaling in the SN of Parkinsonian patients could play a role in the impaired dopaminergic transmission associated with the degenerative disease.
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PMID:Transfection of tyrosine kinase deleted FGF receptor-1 into rat brain substantia nigra reduces the number of tyrosine hydroxylase expressing neurons and decreases concentration levels of striatal dopamine. 1603 6


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