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)

In Huntington's chorea the biochemical disturbances are to some degree a reverse of those observed in Parkinson's disease and a failure of the cholinergic system is prevalent. Former attempts at treatment were based on blockade of the dopaminergic system. The author suggests that the general line of treatment should be -- similarly as in Parkinson's disease -- not blockade of the predominant system but enhancing the cholinergic activity by administration of acetylcholine precursors and agents blocking cholinesterase. Eight patients were treated in this way and significant improvement was achieved in half of them. Further therapeutic trials along these lines are justified theoretically and the main problem will be to find substances crossing the blood-brain barrier and acting more strongly.
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PMID:[New attempt at treating Huntington's chorea (preliminary report)]. 13 May 61

Lumbar cerebrospinal fluid (CSF) acetylcholine (ACh) and choline (Ch) levels were measured in patients with Huntington's chorea (N=11), Parkinson's disease (N=8), and subjects at risk for Huntington's chorea (N=4), and all three groups were found not to differ significantly from normal controls (N=10). The values found for lumbar CSF ACh and Ch levels in the normal subjects were comparable with previously reported values. The use of physostigmine, a cholinesterase inhibitor, in collecting the CSF samples did not appear to make a difference with regard to ACh and Ch concentrations. Evidence suggesting a ventricular-lumbar gradient, with lumbar CSF Ch concentration being less than ventricular CSF Ch concentration, was found. Finally, ACh levels in CSF did not correlate with corresponding Ch levels.
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PMID:Acetylcholine and choline in cerebrospinal fluid of patients with Parkinson's disease and Huntington's chorea. 13 12

Several neurotransmitter markers were investigated in the cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) (n = 27), Parkinson's disease (PD) (n = 35) and ALS (n = 26) and from control subjects (n = 34) to compare the possible alterations in the biochemical profiles of these different neurodegenerative diseases. The main proportion of the patients represented an early phase of the illness at the time of the diagnosis. Correlations of the degree of dementia and the stage of the disease with CSF measures were evaluated. The CSF levels of somatostatin like-immunoreactivity (SLI) were significantly reduced in AD patients when compared with those of normals and ALS patients. The CSF concentrations of homovanillic acid (HVA) were significantly decreased for PD patients and the decrease focused on the non-demented patients. A trend of decreasing HVA values towards the most advanced stage of Parkinson's disease assessed by Webster's scale was also displayed. The content of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF was higher for ALS patients than for other groups. The lowest 5-hydroxy-indoleacetic acid (5HIAA) levels were observed in the PD group and the lowest acetylcholinesterase (AChE) activities were found in the PD patients with the most severe disease. Changes in CSF measures were too subtle to be beneficial for diagnostic purposes, but adequate for reflecting the different neurochemical profiles of these three degenerative neurological disorders.
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PMID:Neurochemical markers in the cerebrospinal fluid of patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and normal controls. 134 20

The mesencephalon of the young domestic pig was studied by tyrosine hydroxylase (TH) immunocytochemistry and acetylcholinesterase (AChE) histochemistry with focus on the substantia nigra (SN), the ventral tegmental area (VTA), and related areas. The purpose was to obtain information on the organization of the mesencephalic, TH immunoreactive (TH-i), and dopaminergic areas of the pig, in order to provide the necessary background for the possible use of the pig as an alternative large animal experimental model for research on Parkinson's disease, including the use of encapsulated pig dopaminergic neurons for intracerebral xenotransplantation. Significant findings in the pig, compared to observations in other species, included the presence of prominent bundles of TH-i dendrites passing in a dorsoventral direction from pars compacta into pars reticulata at middle and caudal levels of the SN, and the presence of a distinct TH-i substantia nigra pars lateralis (SNL). Caudally in the pig mesencephalon, the retrorubral field (RRF) was found to be very extensive. The view of the RRF, SN, and VTA as parts of the same integrated system was indicated by the crisscrossing of TH-i dendrites at the transitions between these areas. Estimation of the number of TH-i neurons in the SN and the VTA showed that these nuclei were of equal size in the pig. Further, it was found that TH-i nerve cells were present in the midline between the VTA in the interfascicular and rostral linear groups. TH-i nerve cells were also present in the otherwise serotoninergic dorsal raphe nuclei, just as other TH-i cells formed a perirubral cell group. AChE-positive neurons were present in both SN and VTA, and appeared to have the same size and morphology as the TH-i neurons in these areas. Within both nuclei, there were local differences in the AChE staining density, but perhaps more significantly were some marked differences in the structure of the AChE-positive neuropil of the two areas. We anticipate that the present description of the cellular organization of the TH-i dopaminergic areas in the domestic pig ventral mesencephalon will be useful for the development of a nonprimate, large animal, experimental model of Parkinson's disease.
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PMID:Tyrosine hydroxylase and acetylcholinesterase in the domestic pig mesencephalon: an immunocytochemical and histochemical study. 135 78

Using the monoclonal antibody, ME 20.4, against the p75 nerve growth factor (NGF) receptor, NGF receptor-like immunoreactivity has been identified in axonal processes innervating the human hippocampus, where previously a loss of reactivity has been reported in a preliminary study of Alzheimer's disease [10]. In an extended analysis of 15 cases of Alzheimer's disease, the number of NGF receptor positive fibres in the fimbria and alveus was generally decreased compared with age-matched normal groups, in presenile but not senile cases (differentiated by age of onset before or after 65 years). By contrast, in 5 demented Parkinson's disease cases (aged 61-86 years at death) immunohistochemically reactive fibres were consistently minimal or absent. This pattern of NGF receptor loss in the hippocampus most closely reflects the loss of basal forebrain cholinergic neurones, previously reported within the different clinical groups but not by biochemical measures of cholinergic function. It is concluded that even at moderately advanced stages of Alzheimer's disease with onset in the senium, axonal processes and NGF receptor mechanisms may be structurally intact in areas of cholinergic innervation from the basal forebrain, despite evidence of cholinergic dysfunction (decreased choline acetyltransferase (ChAT) and acetylcholinesterase), but that in presenile Alzheimer's and in demented Parkinson's disease cases the receptor declines in conjunction with the loss of subcortical neurones and their processes. The loss of ChAT activity may therefore reflect a dysfunction of the NGF system, in its normal maintenance of the cholinergic phenotype in basal forebrain neurones.
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PMID:Hippocampal nerve growth factor receptor immunoreactivity in patients with Alzheimer's and Parkinson's disease. 143 50

The enzymatic activity of acetylcholinesterase (AchE) in the cerebrospinal fluid (CSF) is considered to be a marker of central cholinergic neuron integrity. Then, we evaluated CSF AchE activity in 90 cases of neurological diseases involving cholinergic system and their related disease, and 28 control cases without central organic lesions or abnormal findings in routine CSF study. AchE activity was evaluated according to Ellman's method using acetylthiocholine iodide as a substrate and tetraisopropyl-pyrophosphoramide, a specific inhibitor of butyrylocholinesterase. CSF AchE of Alzheimer type dementia (AD/SDAT, N = 12: 21.9 +/- 4.7 nmol/ml/min) showed no significant change from those of both control group (22.1 +/- 3.9) and vascular dementia (9: 21.7 +/- 6.7). In extrapyramidal diseases, reduction of the activity was observed in Huntington's chorea (HC, 4: 16.3 +/- 1.4) and progressive supranuclear palsy (PSP, 4: 17.6 +/- 1.7), whereas normal activity was shown in Parkinson's disease (PD, 19: 22.5 +/- 4.6), dentatorubropallidoluysian atrophy (DRPLA, 4: 22.6 +/- 4.2) and striatonigral degeneration (SND, 4: 20.4 +/- 4.3). In olivopontocerebellar atrophy (OPCA, N = 16), we disclosed reduced CSF AchE activity (15.8 +/- 2.4) which had significant correlations with the atrophy of the pontine base (r = 0.6017, p less than 0.02) and cerebellar vermis (r = 0.5450, p less than 0.05) in MRI. AchE activity in cerebellar cortical atrophy (CCA, 5: 20.6 +/- 2.2) remained within the control values. Normal activity was demonstrated in both amyotrophic lateral sclerosis (6: 24.3 +/- 7.3) and spinal muscular atrophy (4: 22.9 +/- 3.9).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[CSF acetylcholinesterase activity in central neurological diseases involving cholinergic systems]. 162 49

The present paper describes the determination of muscarinic receptor number ([3H]-N-methylscopolamine binding) and acetylcholinesterase activity in six brain areas (pre-central gyrus, post-central gyrus, hippocampus, caudate nucleus, lentiform nucleus and substantia innominata) of demented patients (diagnosed by screening tests and neurological evaluation) and age-matched controls. There was a significant increase in muscarinic receptors in the hippocampus and substantia innominata (171.2 and 359.4 fmol/mg protein, respectively) of the demented group as compared with controls (123.9 and 219.0 fmol/mg protein, respectively). No changes were observed in pre- and post-central gyrus, while a tendency towards decreased binding was detected in the caudate nucleus and lentiform nucleus of the demented group. Lower acetylcholinesterase activity was also detected in the demented group in all areas studied although the differences were significant only in the post-central gyrus, caudate nucleus and substantia innominata which showed a 49, 21 and 25% decrease in enzyme activity, respectively. The results are discussed in terms of a compensatory mechanism of presynaptic deficiency such as that occurring in Parkinson's disease.
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PMID:Muscarinic receptors and acetylcholinesterase activity in brain of patients with dementia. 182 16

In a effort to better define the role cholinergic basal forebrain neurons play in human cognitive processes, a quantitative assessment of cholinergic nucleus basalis (Ch4) neurons was carried out in 5 patients with Parkinson's disease (PD; 4 non-demented and 1 demented) and 4 age-matched controls using nerve growth factor (NGF) receptor immunohistochemistry as a direct marker for cholinergic basal forebrain neurons. Virtually all (greater than 90%) NGF receptor-containing neurons co-localize with the specific cholinergic marker choline acetyltransferase (ChAT) within the nucleus basalis in PD. NGF receptor-containing neurons were reduced on average by 68% (range 38.6-87.4%) in the non-demented PD cases and by 88.6% in the demented PD patient. Loss of these neurons was heterogeneous across the nucleus basalis subfields with only the anterolateral and posterior Ch4 subregions demonstrating significant reductions of NGF receptor-containing neurons. The reduction in NGF receptor-containing neurons was accompanied by a decrease of acetylcholinesterase (AChE) containing fibers within temporal cortex and in some cases ChAT immunoreactivity in the basolateral amygdaloid nucleus. The numerous non-cholinergic AChE-rich pyramidal cells which were observed throughout the cortex of aged controls were also virtually absent in PD. Although PD patients exhibited severe reductions in Ch4 neurons, few neuritic plaques or neurofibrillary tangles were observed within the PD cortex or Ch4 and similar numbers of these AD-type pathologies were seen within age-matched controls. This suggests that Ch4 degeneration alone is not sufficient to induce such cytoskeletal abnormalities and that the neuron loss seen within Ch4 in AD and PD may be mediated through different processes. These results, coupled with the extensive basic and clinical literature linking acetylcholine and memory function, further indicate that Ch4 degeneration without additional cortical and/or subcortical pathology is not sufficient to impair cognition in PD. Perhaps additional pathology must be superimposed upon nucleus basalis degeneration to induce dementia in humans.
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PMID:Nerve growth factor receptor immunoreactivity within the nucleus basalis (Ch4) in Parkinson's disease: reduced cell numbers and co-localization with cholinergic neurons. 184 79

The autoradiographic distribution of D1 dopaminergic binding sites was studied in the human ventral mesencephalon using the D1 antagonist [3H]SCH 23390. [3H]SCH 23390 binding was characterized by a single class of sites with a Kd of 2.5 nM and a Bmax of 31 fmol/mg of tissue. The density of [3H]SCH 23390 binding sites was high in the substantia nigra, moderate in the ventral tegmental area and low in the peri- and retrorubral field (catecholaminergic region A8). Binding densities were similar in pars compacta and pars reticulata of the substantia nigra, except for a peak value of high [3H]SCH 23390 in the pars reticulata, at a level just ventral to a zone of hyperdensity of melanized dopaminergic neurons in the pars compacta. The anatomical organization of the human ventral mesencephalon was analysed on adjacent sections stained for acetylcholinesterase histochemistry and tyrosine hydroxylase, substance P, dynorphin B, somatostatin and methionine-enkephalin immunohistochemistry, respectively. The similarity in distribution of [3H]SCH 23390 binding sites and substance P or dynorphin B immunoreactivity suggests that D1 binding sites are mainly located on the striatonigral projections. In accordance with these results: (1) the density of [3H]SCH 23390 binding sites was reduced in the substantia nigra of a patient with Huntington's chorea, a disease associated with a degeneration of striatonigral neurons; (2) the density of [3H]SCH 23390 binding sites was unaffected in the substantia nigra of a patient with Parkinson's disease, a disorder characterized by a marked loss in nigral tyrosine hydroxylase-positive neurons. [3H]SCH 23390 binding sites showed a characteristic, heterogeneous distribution within the human ventral mesencephalon, confirming data obtained in other species. The preferential localization of D1 dopamine receptors on striatonigral projections in human brain suggests that pharmacological manipulation of these receptors modulates the activity of striatonigral pathways, thereby affecting the various outputs of the nigral complex.
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PMID:Microtopography of D1 dopaminergic binding sites in the human substantia nigra: an autoradiographic study. 198 69

Mouse 3T3 fibroblasts were genetically modified by transfection with a mammalian expression vector containing the rat beta-nerve growth factor (NGF) gene. The transfected cell line, designated 3E, contains several hundred copies of the rat NGF gene and secretes high levels of biologically active NGF. Pieces of collagen gel containing the NGF-secreting 3E cells were grafted to the brains of unilaterally fimbria-fornix-lesioned rats. Grafts of the genetically modified NGF-producing cells rescued axotomized basal forebrain cholinergic neurons and significantly reduced cholinergic cell death in the medial septum as compared with rats treated with grafts of the parental 3T3 cells. Grafted fibroblast cells were detected, and rescue effects were noted up to 6 weeks after grafting. Local effects of NGF secreted by grafted cells were also seen at the gel-brain border in the form of sprouting acetylcholinesterase immunoreactive host cortical fibers. We suggest that implantation of genetically modified cells producing NGF may have therapeutic applications in rescuing damaged central cholinergic neurons in senile dementia of the Alzheimer type as well as in providing trophic support for chromaffin tissue grafts in Parkinson's disease.
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PMID:Rescue of basal forebrain cholinergic neurons after implantation of genetically modified cells producing recombinant NGF. 232 66


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