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)

The glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), S100 protein (S100), gamma gamma-enolase and neurofilament proteins were determined in the CSF of neurological patients. In Alzheimer's disease (AD), the GFAP values were very often increased but this was not specific to this disease. In 2 cases of familial AD, increases in neurofilament protein were detected. The determination of autoantibodies against neurofilament proteins in blood showed rather low values in AD, although they were higher than in subacute sclerosing panencephalitis (SSPE) and Chagas' disease. Increases were observed in diseases not related to AD such as vascular disorders and Parkinson's disease.
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PMID:Blood and cerebrospinal fluid anomalies in brain ageing and Alzheimer's disease. 244 27

A primary neuronal culture was prepared from the ventral mesencephalon, centered on the A8, A9 and A10 dopaminergic nuclei of the embryonic day 14 rat, and studied from 12 h to 28 days. At 12 h after plating, and before cell death ensued, 95% of the cells stained positive for neuron specific enolase; 20% for tyrosine hydroxylase; 5% for vimentin and < 0.1% for glial fibrillary acidic protein. In the presence of the mitotic inhibitor cytosine arabinoside (2.0 microM), neuronal growth and survival were surprisingly normal up to the ninth day in culture, but deteriorated rapidly thereafter. In the absence of a mitotic inhibitor, and in the presence of proliferating but non-confluent glia, the tyrosine hydroxylase positive neurons that survived to the 10th day, had retracted neurites and a rounded soma, suggesting an inhibition of cell development. Those tyrosine hydroxylase positive neurons that survived this adverse phase of development tended to produce elaborate neuritic profiles after the 11th day, coincident with confluence of the astrocyte monolayer at the 12th day. By the 21st day in culture, and persisting up to the 28th day, 60% (61 +/- 10, n = 20) of the surviving neurons stained positive for tyrosine hydroxylase. When plated on an established, ventral mesencephalic monolayer of astrocytes, at the seventh day in culture, neuritic growth and branching of the tyrosine hydroxylase positive neurons were greater, compared with similar neurons grown on poly-D-lysine, and the signs of arrested development (retraction of neurites and rounded soma) seen at the 10th day after plating on poly-D-lysine, were not observed. We conclude that in the primary culture studied, and under the experimental conditions used, the survival of dopaminergic neurons was independent of glia during the first nine days, and critically dependent on glia thereafter. The resurgence of growth of dopaminergic neurons after 10 days in vitro, and their subsequent selective survival in culture, suggest that confluent type-1 astrocytes produce factors that act selectively on the dopaminergic neuronal phenotype. The successful identification of these dopaminergic-specific, neurotrophic factors could lead to an increased understanding of the etiology of Parkinson's disease, and suggest new directions for therapeutic intervention.
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PMID:Astrocyte-dependent and -independent phases of the development and survival of rat embryonic day 14 mesencephalic, dopaminergic neurons in culture. 793 1

The use of primary human fetal tissue in the treatment of neurodegenerative disorders, while promising, faces several difficult technical and ethical issues. An alternative approach that would obviate these problems would be to use immortalized cell lines of human fetal central nervous system origin. An immortalized human fetal astrocyte cell line (SVG) has been established (45) and herein we describe the in vitro and in vivo characteristics of this cell line which suggest that it may be a useful vehicle for neural transplantation. The SVG cell line is vimentin, GFAP, Thy 1.1 and MHC class I positive, and negative for neurofilament and neuron specific enolase, consistent with its glial origin. To determine whether the cell line could be used as a drug delivery system, a cDNA expression vector for tyrosine hydroxylase was constructed (phTH/Neo) and stably expressed in the SVG cells for over 18 months as demonstrated by immunohistochemistry and Western blotting of the stable transfectants. HPLC analysis of the supernatant from these cells, termed SVG-TH, consistently found 4-6 pmol/ml/min of l-dopa produced with the addition of BH4 to the media. Furthermore, in cocultivation experiments with hNT neurons, PC-12 cells and primary rat fetal mesencephalic tissue, both the SVG and SVG-TH cells demonstrated neurotrophic potential, suggesting that they constituitively express factors with neuroregenerative potential. To determine the viability of these cells in vivo, SVG-TH cells were grafted into the striatum of Sprague-Dawley rats and followed over time. A panel of antibodies was used to unequivocally differentiate the engrafted cells from the host parenchyma, including antibodies to: SV40 large T antigen (expressed in the SVG-TH cells), human and rat MHC class 1, vimentin, GFAP, and tyrosine hydroxylase. While the graft was easily identified with the first week, over the course of a four week period of time the engrafted cells decreased in number. Concomittantly, rat CD4 and CD8 expression in the vicinity of the graft increased, consistent with xenograft rejection. When the SVG-TH cells were grafted to the lesioned striatum of a 6-hydroxydopamine lesioned rats, rotational behavior of the rat decreased as much as 80% initially, then slowly returned to baseline over the next four weeks, parallelling graft rejection. Thus, the SVG-TH cells can induce a functional recovery in an animal model of Parkinson's disease, however as a xenograft, the SVG cells are recognized by the immune system.
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PMID:Expression of tyrosine hydroxylase in an immortalized human fetal astrocyte cell line; in vitro characterization and engraftment into the rodent striatum. 868 28

The study was made of 17 patients with expected Alzheimer's disease (AD), 29 patients with Parkinson's disease (PD) and 7 with a expected dementia with Levy bodies (DLB). The severity of cognitive disorders was determined according to the following scales: Global Deterioration Rating Scale, Mini-mental State Examination, Mattis Dementia Rating Scale. Besides, the patients state was evaluated, in the whole, according to some scales. Permeability of hemato-encephalic barrier was evaluated according to the blood serum levels of 3 neurospecific proteins--neuron specific enolase, glial fibrillary protein and alpha-glycoprotein. Their determination was performed by ELISA method. The significant elevation of the levels of the proteins studied was found already on the early stages of the disease. Their levels were higher in the patients with the dementia as compared with the individuals without it. There were no differences in cortical, subcortical and combined types of dementia. The authors believe, that some of the proteins studied (neuron specific enolase, for example) may serve as non specific markers of cerebral degeneration.
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PMID:[Permeability of hemato-encephalic barrier in Alzheimer's disease and parkinsonism with cognitive disorders]. 1150 13

The experiment was to evaluate the therapeutic benefit of transplanted bone marrow stromal cells (BMSCs) transfected with a kind of neurotrophic factor gene, neurturin (NTN) gene, in treating the rat model of Parkinson's disease (PD). The 6-OHDA-lesioned rats were assigned to one of three groups, those receiving BMSCs transfected with NTN gene, those receiving untransfected BMSCs containing a void plasmid and those receiving phosphate buffer solution (PBS). Treatments were injected into the right striatum (6-OHDA-lesioned side). One to six months post-transplantation, apomorphine-induced rotational behavior was observed. One month after transplantation, green fluorescent protein (GFP)/NTN, GFP/glial fibrillary acidic protein (GFAP), GFP/neuron specific enolase (NSE) and GFP/tyrosine hydroxylase (TH) fluorescence determinations of brain sections were carried out. One to six months after transplantation, brain sections containing striatum and substantia nigra were stained for TH. In situ hybridization and Western blots were used to determine NTN mRNA and protein concentration, respectively, in affected brain regions. High performance liquid chromatography (HPLC) was used to measure the dopamine (DA) content in the lesioned striatum 1 and 3 month(s) post-transplantation. The results were shown that: in the first 3 months after transplantation, the number of rotations was lower in NTN-transplant group than the void vector group, and during 1-6 months post-transplantation, the number of rotations was lower in both transplant groups than that in the PBS group (P<0.05). One month after transplantation, we detected GFP/NTN-, GFP/GFAP- and GFP/NSE-labeled cells in the transplantation area of the NTN-transplanted group, but no obvious GFP/TH labeled cells were found. Quantitative analysis of TH-positive cells 1 to 6 months after transplantation indicated that there were no significant differences between groups in survival rates of TH-positive neurons in the lesioned substantia nigra (P>0.05). In situ hybridization and Western blot identified NTN mRNA and protein expression in the transplantation area of the NTN-transplanted group. After transplantation of NTN-expressing cells, DA content in the lesioned striatum was significantly higher in the transgenic group than that in the void vector group or the PBS group (P<0.05). The overall therapeutic effects of the NTN-transplanted group were superior to those of the void plasmid group and the PBS group. The mechanisms by which transgenic therapy treats PD might involve functional enhancement of residual dopaminergic neurons by NTN, which significantly reduces the number of rotations in animals, but not increase the numbers of existing dopaminergic neurons.
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PMID:Transplantation of bone marrow stromal cells containing the neurturin gene in rat model of Parkinson's disease. 1733 73

Midbrain dopamine (DA) neurons play an essential role in modulating motor control. Defects in central DA neurons affect a wide range of neurological disorders including Parkinson's disease (PD). The greatest motivation in the field has been the potential use of DA neurons for cell transplantation therapy in Parkinsonian patients. Recent studies indicated that BMSCs could differentiate into DA neurons in vitro as neural stem cells (NSC) and embryonic stem cells (ESC) could. However, there are no direct evidences about functional DA neurons derived from BMSCs. According to the protocols which had been applicated in inducing neuronal stem cells and embryonic stem cells differentiate into DA neurons in vitro, the present study provides a protocol by using 50 micromol/L brain derived neurotrophy factor (BDNF), 10 micromol/L forskolin (FSK) and 10 micromol/L dopamine (DA) to induce BMSCs differentiate into DA neurons. After 2 weeks of differentiation, the cells expressed the character of neurons in ultrastructure. RT-PCR discovered mRNA of NSE (neuron specific enolase), Nurr1, Ptx3, Lmx1b and Tyrosine hydroxylase (TH) were positive. Immunocytochemistry staining indicated the ratio of TH-positive neural cells was significantly increased after induced 2 weeks (24.80 +/- 3.36) % compared to that of induction of 3 days (3.77 +/- 1.77) %. And the DA release was also different between differentiated and undifferentiated cells detected by high performance liquid chromatography (HPLC). That is to say BDNF and FSK and DA can induce BMSCs differentiate into DA neurons in vitro, and the transdifferentiated cells express mature neurons characters. BMSCs might be a suitable and available source for the in vitro derivation of DA neurons and cell transplantation therapy in some central neural system diseases such as PD.
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PMID:[Human bone marrow mesenchymal stem cells differentiated into dopaminergenic neurons in vitro]. 1746 Aug 97

L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.
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PMID:Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced dyskinesia. 1753 90

Altered expression and mutations in alpha-synuclein (alpha-syn) have been linked to Parkinson's disease (PD) and related disorders. The neurological alterations in PD patients have been associated with degeneration of dopaminergic cells and other neuronal populations. Moreover, recent studies in murine models have shown that alterations in neurogenesis might also contribute to the neurodegenerative phenotype. However, the mechanisms involved and the effects of alpha-syn expression on neurogenesis are not yet clear. To this end, murine embryonic stem (mES) cells were infected with lentiviral (LV) vectors expressing wild-type (WT) and mutant alpha-syn. Compared with mES cells infected with LV-green fluorescent protein (GFP), cells expressing WT and mutant alpha-syn showed reduced proliferation as indicated by lower 5-bromo-2'-deoxyuridine uptake, increased apoptosis, and reduced expression of neuronal markers such as neuron specific enolase and beta-III tubulin. The alterations in neurogenesis in alpha-syn-expressing mES cells were accompanied by a reduction in Notch-1 and Hairy and enhancer of split-5 (Hes-5) mRNA and protein levels. Moreover, levels of total Notch-1 and Notch intracellular domain (NICD) were lower in mES cells expressing WT and mutant alpha-syn compared with GFP controls. The reduced survival of alpha-syn-expressing mES cells was reverted by overexpressing constitutively active NICD. Similarly, in alpha-syn transgenic mice, the alterations in neurogenesis in the hippocampal subgranular zone were accompanied by decreased Notch-1, NICD, and Hes-5 expression. Together, these results suggest that accumulation of alpha-syn might impair survival of NPCs by interfering with the Notch signaling pathway. Similar mechanisms could be at play in PD and Lewy body disease.
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PMID:Alpha-synuclein alters Notch-1 expression and neurogenesis in mouse embryonic stem cells and in the hippocampus of transgenic mice. 1841 5

Parkinsonian disorders such as Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a large group of common neurodegenerative diseases. The initial differential diagnosis can be extremely challenging with major implications for prognosis. The 42 amino acid fragment of amyloid-beta (Abeta42), neurofilament light chain (NFL), neurofilament heavy chain (pNFH), tau protein, glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), S-100B protein, and myelin basic protein (MBP) are brain related proteins (BRP) present in neurons and glia cells. They are released in the cerebrospinal fluid (CSF) after brain tissue damage caused by a variety of neurological diseases, including the parkinsonian disorders. A review of the literature shows that, carefully interpreted, the CSF levels of BRP can be of value in the differential diagnosis of parkinsonian disorders.
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PMID:Levels of brain related proteins in cerebrospinal fluid: an aid in the differential diagnosis of parkinsonian disorders. 1856 38

Protein glycation is involved in structure and stability changes that impair protein functionality, which is associated with several human diseases, such as diabetes and amyloidotic neuropathies (Alzheimer's disease, Parkinson's disease and Andrade's syndrome). To understand the relationship of protein glycation with protein dysfunction, unfolding and beta-fibre formation, numerous studies have been carried out in vitro. All of these previous experiments were conducted in non-physiological or pseudo-physiological conditions that bear little to no resemblance to what may happen in a living cell. In vivo, glycation occurs in a crowded and organized environment, where proteins are exposed to a steady-state of glycation agents, namely methylglyoxal, whereas in vitro, a bolus of a suitable glycation agent is added to diluted protein samples. In the present study, yeast was shown to be an ideal model to investigate glycation in vivo since it shows different glycation phenotypes and presents specific protein glycation targets. A comparison between in vivo glycated enolase and purified enolase glycated in vitro revealed marked differences. All effects regarding structure and stability changes were enhanced when the protein was glycated in vitro. The same applies to enzyme activity loss, dimer dissociation and unfolding. However, the major difference lies in the nature and location of specific advanced glycation end-products. In vivo, glycation appears to be a specific process, where the same residues are consistently modified in the same way, whereas in vitro several residues are modified with different advanced glycation end-products.
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PMID:Protein glycation in vivo: functional and structural effects on yeast enolase. 1865 35


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