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 scanning nuclear microprobe (nuclear microscope) is becoming a powerful instrument for the accurate measurement of minor and trace elements in biological tissue. Using the simultaneously applied techniques of Scanning Transmission Ion Microscopy (STIM) to image features in the tissue, Particle induced X-ray emission (PIXE) to measure trace element concentrations, and Rutherford Backscattering Spectrometry (RBS) to characterize the tissue matrix, accurate elemental analysis at the parts per million level can be obtained for most elements. This review describes briefly the results obtained using the nuclear microscope for the elemental analysis of Alzheimer's and Parkinson's tissue. In Alzheimer's disease (AD) the identification and subsequent analysis of neuritic plaque cores in unstained tissue, yielded an absence of aluminium at the limit of 15 parts per million. Previous analyses involving stained sections were prone to misinterpretation due to aluminium contamination from the staining procedures. Elemental iron, calcium, phosphorus and sulphur were elevated both in the plaques and the AD background tissue compared to age matched controls. Preliminary analyses of neurofibrillary tangles stained with toluidine blue showed increased levels of calcium, although the staining procedure may have distorted the results due to element redistribution. In Parkinson's disease (PD) nuclear microscope studies have concentrated on measurements of iron in the substantia nigra (SN) region of the brain; iron was observed to be elevated by a factor 2 in MPTP induced Parkinsonism in African Green monkeys, and by a factor of 1.25 in 6-OHDA induced Parkinsonism in Sprague Dawley rats. These studies are consistent with other studies showing a general increase in the concentrations of iron associated with PD, and support the theory that iron mediated free radical production may enhance or accelerate the degeneration of dopaminergic cells through oxidative stress.
Cell Mol Biol (Noisy-le-grand) 1996 Feb
PMID:Nuclear microscope analysis in Alzheimer's and Parkinson's disease: A review. 883 63

We have now applied the enzyme immunoassay using anti-NGF monoclonal antibody (MAb) 27/21 and a blocking test validating the specificity of the immunoreactivity for NGF in serum samples to examine NGF levels in normal rat sera, hemiparkinsonian rat sera, normal monkey sera, and MPTP-treated monkey sera. The levels of NGF in treated animals showed reductions when compared with serum from normal animals. The NGF level alterations observed in lesioned animals and in human parkinsonian patients evidence a relationship between this neurotrophic factor and the neurodegenerative changes observed in Parkinson disease (PD).
Mol Chem Neuropathol
PMID:NGF in experimental models of Parkinson disease. 887 63

Nurr1 and NGFI-B are closely related orphan members of the steroid-thyroid hormone receptor family involved in immediate early responses to stimuli such as growth factors. In-situ hybridization in the developing and adult mouse and rat demonstrated Nurr1 mRNA in several regions during early central nervous system (CNS) development. Expression persisted through the pre- and postnatal periods and was also found in several areas in the adult CNS. Positive areas include the olfactory bulb, parts of the cortex, the hippocampal formation and substantia nigra where Nurr1 and tyrosine hydroxylase mRNAs were co-expressed. 6-Hydroxydopamine-induced degeneration of mesencephalic dopamine neurons led to a corresponding loss of Nurr1 mRNA, demonstrating a link between Nurr1 and dopaminergic neurons. NGFI-B mRNA was not found in the prenatal CNS but was highly expressed in the adult brain in many areas including the olfactory bulb, cortex, basal ganglia and hippocampus. The spatiotemporal distribution of Nurr1 and NGFI-B mRNAs suggests that these transcription factors are involved in the development and maturation of specific sets of CNS neurons. The experimental data imply that one of these functions may be to control gene regulatory events important for development and function of those neurons that degenerate in patients with Parkinson's disease.
Brain Res Mol Brain Res 1996 Sep 05
PMID:Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system. 888 41

The cellular expression of DAT mRNA and VMAT2 mRNA was investigated in sections of the human post-mortem substantia nigra in control and Parkinson's disease tissue using in situ hybridisation techniques. Short synthetic oligodeoxynucleotides were used to detect these gene transcripts at the cellular level. In the control human nigra, high levels of expression were seen in all sub-divisions of the substantia nigra, especially within medial regions. By contrast, the level of expression of both DAT mRNA and VMAT2 mRNA was markedly reduced in Parkinson's disease; these reductions in hybridisation signal were associated with (i) a marked loss of dopamine-containing cells in the substantia nigra, and (ii) a reduction in both DAT and VMAT2 signal per cell in the remaining pigmented neurones. These disease-related decreases in the cellular abundance of both DAT and VMAT2 gene transcripts in the surviving cells of the parkinsonian nigra may reflect compensatory changes in catecholamine signalling or may be a consequence of neuronal dysfunction.
Brain Res Mol Brain Res 1996 Feb
PMID:Dopamine transporter (Dat) and synaptic vesicle amine transporter (VMAT2) gene expression in the substantia nigra of control and Parkinson's disease. 901 52

We molecularly cloned the kappa opioid receptor from a human substantia nigra cDNA library. When expressed in HEK293 cells, the cloned receptor had similar pharmacological characteristics to the rat kappa opioid receptor. Northern blot analysis showed the presence of a single transcript of about 6 kb in size for mRNA prepared from the substantia nigra. Using in situ hybridization histochemistry, we studied the expression of this receptor in postmortem human brains from control and Parkinson's disease subjects. Kappa opioid receptor mRNA was present in melanized (possibly dopaminergic) neurons of the substantia nigra and the nucleus paranigralis. On the other hand, Parkinson's disease brains had markedly fewer melanized neurons, as expected, and correspondingly very low or background levels of mRNA for the kappa opioid receptor. However, in some cases, remaining melanized neurons still expressed the receptor mRNA. From these results we suggest that dopaminergic neurons in the human substantia nigra and the nucleus paranigralis synthesize kappa opioid receptors and express them in their perikarya and their terminal regions. The kappa opioid receptor expressed in the melanized neurons may play a role in the normal function of dopaminergic systems and possibly in the etiology of Parkinson's disease.
Brain Res Mol Brain Res 1997 Feb
PMID:The expression of mRNA for a kappa opioid receptor in the substantia nigra of Parkinson's disease brain. 903 Jun 93

Alterations in the number or functional state of D2 dopamine receptors have been implicated in the decreased motor abilities associated with normal aging, Parkinson's disease and other neurodegenerative diseases. Previous work has demonstrated a substantial decrease in D2 receptor-containing neurons, receptor proteins, steady-state mRNA levels, and the rate of mRNA synthesis with age in the rat striatum in particular and in mammalian brains in general. These observations suggest that one key area of regulatory control is at the level of transcriptional initiation and/or elongation. In the present study gel mobility shift experiments were used to assess the interaction of nuclear proteins from different rat brain regions with DNA containing putative DNA regulatory sites of the transcriptionally active rat D2 receptor gene promoter. Oligonucleotides containing either of the two SP1 binding sites immediately upstream of the primary transcriptional start site were bound by proteins found in nuclear extracts obtained from rat striatum, hippocampus, cortex, and cerebellum. Extracts from striatum and hippocampus formed predominantly low molecular weight complexes which do not contain SP1, as well as a small amount of high molecular weight complexes which may contain SP1 or an SP1-related protein. Cerebellar extracts formed two similar sets of complexes, but they were formed in roughly equal amounts. Extracts from cortex produced a more involved pattern of complexes, but still formed both high molecular weight complexes which contain SP1 and low molecular weight complexes which do not contain SP1. There were differences in the gel mobility as well as the relative amounts of complexes formed with the two SP1-specific oligonucleotides among different brain regions. With respect to possible age-related changes in transcription of the D2 dopamine receptor gene, there appeared to be no statistically significant difference in the DNA-protein complexes formed with striatal nuclear proteins from a population of young rats versus a population of old rats.
Brain Res Mol Brain Res 1997 Feb
PMID:Interaction of nuclear factors from young and old rat brain regions with regulatory sequences of the D2 dopamine receptor gene promoter. 903 Jul 5

The involvement of abdominal afferent vagal activity and serotonergic mechanisms were examined following intravenous administration of talipexole, a dopamine D2 receptor agonist used for treatment of Parkinson's disease, in anesthetized rats. Intravenous administration of dopamine receptor agonists including D1/D2 components increased the spontaneous firing of afferent vagal neurons as did 2-methyl-5-hydroxytryptamine. Both talipexole (0.25-1.0 mg/kg) and bromocriptine (1.0-10.0 mg/kg) increased vagal nerve activity in a dose-dependent manner, and the effect of 10 mg/kg of bromocriptine was significantly greater than that noted with 1.0 mg/kg of talipexole. Increasing vagal firing induced by talipexole was prevented by pretreatment with granisetron, but not with metoclopramide or by spinal section, indicating that afferent vagal firing was mediated via stimulation of the 5-HT3 receptors on the neurons and secondarily caused by stimulation of dopamine receptors. On the other hand, bromocriptine at 5 mg/kg increased 5-HIAA concentration in the ileum, and serotonin turnover (5-HIAA/5-HT) was increased approximately 4-fold when compared to the vehicle group. Bromocriptine also increased the activities of tryptophan hydroxylase and monoamine oxidase. Talipexole at 0.5 mg/kg did not affect ileal 5-HT metabolism and the enzymatic activities. These findings suggest that dopamine receptor agonists may induce changes in abdominal afferent vagal activity and ileal 5-HT metabolism similar to those observed with emetic compounds, and that talipexole has a much smaller influence on serotonin-mediated responses than does bromocriptine with equipotent antiparkinsonian doses. One of the possible reason why talipexole showed fewer emetic side effects in patients with Parkinson's disease may be that the emetic responses triggered by D2 receptor stimulation may secondarily cause an increase of abdominal afferent vagal activity, which may be weakened by the 5-HT3 receptor antagonistic property of talipexole.
Res Commun Mol Pathol Pharmacol 1997 Jan
PMID:Effects of talipexole on emesis-related changes in abdominal afferent vagal activity and ileal serotonin metabolism in rats. 905 50

L-Deprenyl, a monoamine oxidase B (MAO-B) inhibitor, administered prior to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) protects dopaminergic neurons against degeneration in several animal species including mice. L-Deprenyl inhibits MPP+ formation, the mediator of MPTP toxicity. In addition, L-deprenyl, administered 72 h following MPTP, improves the recovery of tyrosine hydroxylase (TH) immunopositive neurons in the substantia nigra (SN) of mice. This observation lead to the proposal that L-deprenyl exerts a 'neurorescue' effect. However, clinical trials failed to demonstrate that L-deprenyl can effectively 'rescues' degenerating dopaminergic neurons in early untreated Parkinson's disease (PD) patients. These observations prompted us to reevaluate the long-term impact of L-deprenyl on MPTP-induced dopaminergic cell loss in mice. In addition, we made use of another MAO-B inhibitor, MDL72974, to assess MAO-B participation in this paradigm. Our results suggest that L-deprenyl does not improve the recovery of TH immunopositive neurons in MPTP-treated mice. An apparent reduction in TH+ neurons is observed in the SN of MDL72974 and L-deprenyl/MPTP-treated mice at 30 days post-treatment. The possible implication of these findings in relation to the used of MAO-B inhibitors in PD is discussed.
Brain Res Mol Brain Res 1997 Mar
PMID:L-Deprenyl and MDL72974 do not improve the recovery of dopaminergic cells following systemic administration of MPTP in mouse. 907 65

Chromogranin A was purified from post-mortem human brain tissue, obtained at autopsy by a three step chromatography procedure to a single band purity on SDS gel electrophoresis at 68 kDa. Purified protein was further characterized by immunoblotting using a mouse anti-chromogranin A monoclonal antibody LK2H10, which recognizes the 68 kDa chromogranin A in human brain. The results demonstrate a simple protocol of preparing CgA from the human brain. Chromogranin plays a very important role in various neurological disorder and has been examined immunohistochemically in Alzheimer's disease, Parkinson's disease, Pick's disease. The procedure of purification may be useful in further defining its biological function, biochemistry and physiological significance in the central nervous system and may be useful in delineating the molecular pathology of certain neurological disorders.
Biochem Mol Biol Int 1997 Mar
PMID:Purification and partial characterization of chromogranin-A from human brain. 909 Apr 64

Dopamine acts, under appropriate conditions, as a selective neurotoxin. This toxicity is attributed to the autoxidation of the neurotransmitter into a reactive quinone that covalently modifies cellular macromolecules (i.e. proteins and nucleic acids). The oxidation of the catecholamine to a quinone is greatly accelerated by the enzyme tyrosinase. There is controversy, however, as to whether or not tyrosinase is expressed in human brain. In the present study, RT-PCR was utilized to demonstrate the presence of tyrosinase mRNA in post-mortem human brain tissues. Using gene-specific amplification primers, specific tyrosinase amplicons were detected following analysis of RNA from substantia nigra of four individuals. Analysis of cerebellar RNA from the same individuals produced no amplification products. Control reactions performed in the absence of reverse transcriptase failed to generate PCR products for any tissue tested. Three amplicons were subjected to direct DNA sequencing and all proved to be identical with tyrosinase sequences, thus obviating the possibility of amplification of a related gene. It is clear, therefore, that the tyrosinase gene is expressed in the human substantia nigra, lending support to previous studies describing tyrosinase-like activity and immunoreactive protein in the brain. This enzyme could be central to dopamine neurotoxicity as well as contribute to the neurodegeneration associated with Parkinson's disease.
Brain Res Mol Brain Res 1997 Apr
PMID:Tyrosinase mRNA is expressed in human substantia nigra. 910 85


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