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 changes in prolactin release induced by acute doses of L-Dopa + benserazide (250 mg) were analysed in Parkinson disease patients undergoing various drug treatments. The results obtained indicate a highly significant increase in prolactinaemia after 60 minutes in a patient undergoing chronic L-Dopa + benserazide therapy, compared to both healthy subjects and patients receiving other drugs. A patient receiving L-Dopa with no inhibitor also showed significantly high prolactinaemia levels after 180 mins. This confirms the hypothesis that elderly Parkinson patients suffer from chronic denervation of the hypothalamic receptors even when no Dopa-decarboxylase inhibitor is present.
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PMID:[Exploration of the tubero-hypophyseal dopaminergic system in patients with chronic parkinsonism during chronic treatment with L-DOPA]. 665 27

A subacute treatment, 500 mg/kg I.P. twice daily during 5 days, by L-methionine provoked an increase in the Bmax of [3H]-spiperone binding in the striatum of the rat. This increase was associated to a decrease in membrane microviscosity. However in these conditions no changes were found in the [3H]-DHA, [3H]QNB bindings or in the brain dopamine sensitive adenylate cyclase activity. L-methionine treatment reduced the accumulation of Dopa after NSD 1015 and antagonized the decrease in striatal acetylcholine provoked by haloperidol. Thus L-methionine might be a new potential drug for Parkinson's disease treatment.
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PMID:A subacute treatment of L-methionine induces an increase in the number of [3H]spiperone binding sites in the striatum of the rat. 684 97

Tyrosine and tryptophan have been assayed spectrofluorometrically in postmortem human brain areas of patients with Parkinson's disease treated orally with or without 3,4-dihydroxyphenylalanine (L-dopa) plus the peripherally acting decarboxylase inhibitor benserazide. Tyrosine as well as tryptophan decrease significantly after treatment with L-dopa, thus showing a competitive action of L-dopa to other aromatic amino acids on human brain uptake. It is suggested that some of the side effects of L-dopa treatment in Parkinson's disease are due to a disturbance in the brain and neural uptake of other, specially aromatic and branched-chain amino acids. An influence of L-dopa administration on protein synthesis also cannot be excluded.
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PMID:L-dopa competes with tyrosine and tryptophan for human brain uptake. 721 1

Previous studies have used recombinant retroviruses encoding the tyrosine hydroxylase (TH) gene to transduce various cell lines, including fibroblasts (NIH-3T3), a pituitary tumor cell line (AtT20), and a pancreatic endocrine line (RIN). These genetically modified cells, synthesizing either 3,4-dihydroxyphenylalanine, dopamine, or both, are potential donors for treatment of Parkinson's disease. However, the levels of TH protein in such transduced cells have been low and heterogeneous. Using several modified versions of retrovirus vectors encoding TH, we demonstrated that protein stability is an important factor governing levels of TH in NIH-3T3 fibroblasts. Whereas low levels of TH protein were observed in infected NIH-3T3 cells, high levels of a TH-beta gal fusion protein were found. This difference was due to a significantly longer half-life of the TH-beta gal fusion protein relative to TH alone. However, the TH-beta gal fusion protein was found to be enzymatically inactive. We also found that the half-life of the endogenous TH protein in PC-12 cells is sevenfold longer than the TH protein in transduced fibroblasts, implying that a cell-type specific regulator or mechanism may stabilize TH in catecholaminergic cells.
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PMID:The stability of endogenous tyrosine hydroxylase protein in PC-12 cells differs from that expressed in mouse fibroblasts by gene transfer. 750 76

One therapeutic approach to treating Parkinson's disease is to convert endogenous striatal cells into levo-3,4-dihydroxyphenylalanine (L-dopa)-producing cells. A defective herpes simplex virus type 1 vector expressing human tyrosine hydroxylase was delivered into the partially denervated striatum of 6-hydroxydopamine-lesioned rats, used as a model of Parkinson's disease. Efficient behavioral and biochemical recovery was maintained for 1 year after gene transfer. Biochemical recovery included increases in both striatal tyrosine hydroxylase enzyme activity and in extracellular dopamine concentrations. Persistence of human tyrosine hydroxylase was revealed by expression of RNA and immunoreactivity.
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PMID:Long-term behavioral recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylase. 763 5

Overshadowed by a vigorous search for an environmentally-derived toxin that would be possibly relevant for the pathogenesis of idiopathic Parkinson's disease (PD), genetic factors have largely been neglected for this condition during the last two decades. Recent descriptions of kindreds over three or more generations with several family members affected have renewed the interest in genetics of PD. Concurring with this, diagnostic concepts and pathologic criteria for PD and for idiopathic Lewy-body (LB) disease have been reevaluated such that LB-proven parkinsonism is sufficiently differentiated from familial parkinsonism without LB pathology. Surveys on genetic epidemiology in PD have confirmed the 19th century's notion that 10 to 15% of PD index cases report a further family member with PD. These figures were, however, substantiated on a statistical basis only in single surveys when comparisons were made with the numbers of PD relatives in control index cases. Twin studies did not reveal a higher rate of concordance within monozygotic pairs than in dizygotic pairs. Tests of striatal 18-F-Dopa uptake in clinically unaffected mono- and dizygotic co-twins did not alter the ratio between the concordance rates. Though not excluded by the twin studies, multifactorial (or polygenic) inheritance as well as mitochondrial inheritance are at present less likely to cover most of the inheritance pattern in familial LB parkinsonism. Instead, autosomal dominant inheritance with reduced penetrance is the most probable inheritance pattern for most of the reported pedigrees. Molecular genetic investigations have to consider the biochemical basis of the age- and region-specific pathology of PD. The first analyses of linkage and allelic associations gave inconclusive results in sporadic and familial PD. The hunt for metabolic factors that link geno- and phenotype expression in PD will continue.
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PMID:Genetic factors in the etiology of idiopathic Parkinson's disease. 789 71

We studied mitochondrial respiratory chain function in skeletal muscle taken from 27 patients with idiopathic Parkinson's disease (PD; 21 Dopa-treated PD patients and 6 de novo patients), 5 patients with multiple system atrophy (MSA) and from 43 age-matched controls in order to determine the occurrence of mitochondrial respiratory chain abnormalities in parkinsonian syndromes. In our control subjects, we found a significant age-related decrease in the activity of respiratory chain complex I. As compared to carefully age-matched control subjects, activity of complex (NADH:ubiquinone reductase) was significantly lower in muscle mitochondria from patients with PD and MSA and a mean remaining activity < 30% of controls was observed. Mean activities of complexes III (ubiquinol:cytochrome c reductase) and IV (cytochrome c oxidase) were also lower in PD patients than controls, but a low activity (remaining activity < 30% of controls) was observed in only 5 PD patients for complex I and III or I and IV. No deficit in complex II activity (succinate:ubiquinone reductase) was observed. Our results support the hypothesis of a wide-spread mitochondrial complex I deficiency in PD and MSA as compared to age-matched controls, who showed age-related deficiency. This deficit can be found in de novo PD patients as well as in treated patients. The observed respiratory enzyme chain deficiency could not be explained by the dose and duration of L-Dopa or dopaminergic agonist treatment, the severity of the disease, anxiety or depression since no significant correlation was found between these parameters and enzyme complexes activities.
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PMID:Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy. 796 95

Ever since the introduction of levo-3,4-dihydroxyphenylalanine (L-dopa) for the treatment of Parkinson's disease, there has been concern that it might accelerate the degeneration of dopamine neurones. Using rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB), we have studied the effect of chronic L-dopa treatment on the survival of dopamine cells which remain in the ventral tegmental area (VTA) ipsilateral to a 6-OHDA lesion. Following lesion surgery, rats were treated with L-dopa and carbidopa administered in the drinking water for 27 weeks. At the end of the treatment period, the number of dopamine cells remaining in each of the lesioned and intact substantia nigra (SN) and VTA were assessed, using tyrosine hydroxylase immunohistochemistry. Chronic L-dopa treatment resulted in an apparent reduction in the number of dopamine neurones remaining in the VTA ipsilateral to the lesion, whereas it had no effect on the number of dopamine cells remaining in the intact SN and VTA. This finding suggests a possible suppressive effect in vivo of L-dopa on dopamine cells in the midbrain of adult animals that have been previously exposed to 6-OHDA.
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PMID:Suppressive effect of L-dopa on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6-hydroxydopamine. 809 79

A study was undertaken of 14 autopsy cases with pigmented rib cartilage. Twelve of these patients had been treated with levodopa because of Parkinson's disease for at least 6 years, and two had been treated with methyldopa because of essential hypertension for 19 years. Thirty-two percent of the autopsy cases of Parkinson's disease during a recent 70-month period demonstrated pigmented rib cartilage. Only one of them also demonstrated pigmentation of intervertebral disks. No abnormal pigmentation was seen in other sites. The pigment was located in the hyaline matrix of rib cartilage and in necrotic chondrocytes. Levodopa was chromatographically demonstrated within the cartilage of patients with Parkinson's disease, but in both pigmented and unpigmented sites. It is speculated that a pigmented drug metabolite is bound preferentially to the matrix of rib cartilage. Dopa pigmentation only occurs in cartilage and differs in several respects from endogenous and exogenous ochronosis. It appears to be harmless but irreversible.
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PMID:Black cartilage after therapy with levodopa and methyldopa. 819 60

Dystonia is a persistent attitude or posture in one or other of the extremes of athetoid movement. It may take the form of an over-extension or over-flexion of the hand, torsion of the spine, with arching and twisting of the back or forceful closure of the eyes and a fixed grimace. Dystonia is classified into idiopathic and symptomatic dystonia. Idiopathic dystonia is further divided into generalized, focal and segmental dystonia. Generalized dystonia covers classical torsion dystonia, paradoxical dystonia, myoclonic dystonia, dystonia with diurnal variation and Dopa-responsive dystonia. Dystonic tic, paroxysmal dystonia and hypnotic dystonia show a dystonic posture, although they are also accompanied by various other involuntary movements such as athetosis or chorea. Torticollis, writer's cramp or blepharospasm is assigned to the focal dystonia and Meige syndrome to the segmental dystonia. Symptomatic dystonia is observed in various neurological disorders, including cerebrovascular diseases, Parkinson's disease and Wilson's disease.
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PMID:[Dystonia]. 827 58


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