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)

Free radicals are reactive chemical species with an unpaired electron that are produced through a variety of physiologic and pathologic processes. Free radicals have been implicated in a variety of neuropsychiatric conditions, many of which are marked by the gradual development of psychopathologic symptoms and movement disorder. There is evidence that radical-induced damage may be important in Parkinson's disease, tardive dyskinesia, metal intoxication syndromes, and Down's syndrome, and possibly also in schizophrenia, Huntington's disease, and Alzheimer's disease. Although some of this evidence is highly speculative, it may offer an avenue for further understanding and treatment of these conditions.
Arch Gen Psychiatry 1991 Dec
PMID:Oxygen radicals and neuropsychiatric illness. Some speculations. 184 28

Elucidation of the mechanism(s) by which 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+) cause parkinsonism in humans and other primates has prompted consideration of possible endogenous MPTP/MPP(+)-like neurotoxins in the etiology of idiopathic Parkinson's disease. Here we examined inhibition of mitochondrial respiration in vitro and neurotoxicity in rats in vivo produced by beta-carbolinium compounds that are presumed to form following Pictet-Spengler cyclization of serotonin. We also evaluated N-methylisoquinolinium, a putative endogenous neurotoxin, in the same manner. The latter compound exhibited MPP(+)-like mitochondrial respiratory inhibition, whereas the beta-carbolinium compounds, although more potent inhibitors of electron transport, exhibited weak accumulation-dependent enhancement of inhibition in intact mitochondria. It is interesting that the beta-carbolinium compounds inhibited succinate- as well as glutamate-supported respiration, and are best described as inhibitor-uncouplers. The results of partitioning experiments suggest that both the low accumulation potential and the inhibition of succinate respiration may be a consequence of the beta-carboliniums being in equilibrium with neutral "anhydro" bases. Relative to MPP+, all compounds tested had weak dopaminergic uptake activity in vitro and weak dopaminergic toxicity in vivo, consistent with other findings of relatively low neurotoxic potential for presumed endogenous pyridiniums.
J Neurochem 1991 Dec
PMID:Dopaminergic neurotoxicity in vivo and inhibition of mitochondrial respiration in vitro by possible endogenous pyridinium-like substances. 194 Sep 17

Elevated iron concentrations in the substantia nigra (SN) pars compacta have been implicated in the development of idiopathic Parkinson's disease. Because, as a transitional metal, iron promotes free radical formation, the role of iron in the degeneration of the nigrostriatal dopamine neurons in Parkinson's disease has received much attention. This study further investigates the cytotoxic effects of iron in the SN. Various concentrations of FeCl3 (1, 5, and 50 micrograms of Fe3+ in 5 microliters) were unilaterally injected into the SN of adult rats. The two lower doses of iron had no effect on striatal dopamine levels or on the behavioral responses of the rats. However, injection of 50 micrograms of Fe3+ resulted in a substantial selective decrease of striatal dopamine (95%), 3,4-dihydroxyphenylacetic acid (82%), and homovanillic acid (45%), without any change in norepinephrine concentration. Dopamine-related behavioral responses, such as spontaneous movements in a novel space and rearing, were significantly impaired, whereas amphetamine administration induced ipsilateral rotation in the iron-treated rats. The present study indicates that the nigrostriatal dopamine neurons are susceptible to the presence of ionic iron and thus supports the assumption that iron initiates dopaminergic neurodegeneration in Parkinson's disease.
J Neurochem 1991 Dec
PMID:Intranigral iron injection induces behavioral and biochemical "parkinsonism" in rats. 194 Sep 19

Nerve growth factor (NGF) is a member of an expanding family of neurotrophic factors (including brain-derived neurotrophic factor and the neurotrophins) that control the development and survival of certain neuronal populations both in the peripheral and in the central nervous systems. Its biological effects are mediated by a high-affinity ligand-receptor interaction and a tyrosine kinase signalling pathway. A potential use for NGF and its relatives in the treatment of neurological disorders such as Alzheimer's disease and Parkinson's disease requires an understanding of the structure-function relationships of NGF. NGF is a dimeric molecule, with 118 amino acids per protomer. We report the crystal structure of the murine NGF dimer at 2.3-A resolution, which reveals a novel protomer structure consisting of three antiparallel pairs of beta strands, together forming a flat surface. Two subunits associate through this surface, thus burying a total of 2,332 A. Four loop regions, which contain many of the variable residues observed between different NGF-related molecules, may determine the different receptor specificities. A clustering of positively charged side chains may provide a complementary interaction with the acidic low-affinity NGF receptor. The structure provides a model for rational design of analogues of NGF and its relatives and for testing the NGF-receptor recognition determinants critical for signal transduction.
Nature 1991 Dec 05
PMID:New protein fold revealed by a 2.3-A resolution crystal structure of nerve growth factor. 195 7

The adrenergic status was studied through evaluation of platelet alpha 2-adrenoceptor number [( 3H]yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with orthostatic hypotension; (2) Parkinsonians without orthostatic hypotension; and (3) control subjects. In Parkinsonians with orthostatic hypotension, systolic and diastolic blood pressures significantly (P less than 0.05) decreased from 144 +/- 9 and 76 +/- 6 mmHg in the lying position to 95 +/- 12 and 60 +/- 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 +/- 11 pg ml-1, (P less than 0.05) when compared with controls (219 +/- 13 pg ml-1) whereas no difference was noticed in Parkinsonians without orthostatic hypotension (195 +/- 14 pg ml-1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P less than 0.01) lower in Parkinsonians with orthostatic hypotension (0.19 +/- 0.03 microgram kg-1) when compared with Parkinsonians without orthostatic hypotension (0.86 +/- 0.11 microgram kg-1) or with controls (0.68 +/- 0.1 microgram kg-1). Platelet alpha 2-adrenoceptor number was higher in Parkinsonians with orthostatic hypotension (313 +/- 52 fmol mg-1 protein) than in Parkinsonians without orthostatic hypotension (168 +/- 9 fmol mg-1 protein) or in controls (175 +/- 4 fmol mg-1 protein) with no change in Kd. This study demonstrates that in patients with Parkinson's disease, orthostatic hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet alpha 2-adrenoceptor number.(ABSTRACT TRUNCATED AT 250 WORDS)
Eur J Clin Invest 1990 Dec
PMID:Adrenergic supersensitivity in parkinsonians with orthostatic hypotension. 196 23

Experiments are described in which the benzodiazepine portion of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor and the muscarinic cholinergic receptor were investigated in Parkinson's disease and control brains. Tritiated flunitrazepam and tritiated quinuclidinyl benzilate (QNB) were used to locate and quantify the receptors by autoradiographic and homogenate binding techniques. Densitometric analysis of autoradiographs of the basal ganglia allowed comparison of receptor densities in the post-mortem control and parkinsonian tissue, while homogenate binding experiments gave information concerning receptor affinity and maximum binding capacity. The results indicate that: 1) Binding of flunitrazepam to the benzodiazepine receptor is reduced in the lateral segment of the globus pallidus in Parkinson's disease. This suggest that the GABA-ergic pathway from the putamen to the lateral pallidal segment is overactive in Parkinson's disease. 2) Binding of QNB to the cholinergic receptors of the medial pallidal segment is increased in Parkinson's disease. This finding suggests underactivity of the cholinergic pathway from the pedunculopontine nucleus of the medial pallidal segment. 3) Binding of these ligands in the caudate and putamen of Parkinson's disease is not significantly different from controls. We reviewed the literature concerning the activity of these projections in parkinsonian conditions assessed by different methods and discuss here their implications for the pathogenesis of parkinsonian symptoms.
J Neurol Sci 1990 Dec
PMID:Changes in benzodiazepine and acetylcholine receptors in the globus pallidus in Parkinson's disease. 196 2

In a survey to determine the occurrence of Levy bodies in the elderly, the prevalence rate of Lewy body formation was found to be critically dependent on the psychiatric status of control cases. In 131 controls between 51 and 100 years screened to exclude psychiatric and neurological disorders, the Lewy body prevalence rate was 2.3%, but inclusion of cases with psychiatric disorders other than Alzheimer's disease increased the prevalence rate to 9%. An age-related decline in substantia nigra and locus coeruleus neuron numbers was observed in the control group. Brain stem Lewy body formation (found in 3 cases) was not necessarily linked with neuron loss in substantia nigra, though in two of the cases significant locus coeruleus neuron loss was observed. Within the control group, there was no obvious relationship of Lewy body formation to the extent of Alzheimer-type pathology. These findings are compatible with the disease specificity of Lewy bodies and suggest that Lewy body disorders have a relatively short preclinical phase in which Lewy body formation may precede both locus coeruleus and substantia nigra neuron loss. The increase of Lewy body positive cases found when individuals with psychiatric disorders are included in the population surveyed supports the emerging concept of a spectrum of Lewy body diseases ranging from purely psychiatric disorders through combined psychoneurological or neuropsychiatric symptoms, to the classically described neurological disorders of Parkinson's disease.
J Neurol Sci 1990 Dec
PMID:Lewy body prevalence in the aging brain: relationship to neuropsychiatric disorders, Alzheimer-type pathology and catecholaminergic nuclei. 196 7

The overactivity of glutamatergic neurons may underlie some neurodegenerative disorders, including Alzheimer's disease (AD). We explored the relationship between glutamatergic transmission and neurofibrillary tangle formation by measuring [3H]-D-aspartate binding activity and the proportion of neurons containing tangles within individual thalamic nuclei in five AD cases. Five elderly normal and five Parkinson's disease (PD) cases were used as controls. A highly significant correlation between [3H]-D-aspartate binding and tangle counts in Alzheimer's disease suggests that those thalamic nuclei which normally receive a relatively dense glutamatergic afferent input are predisposed to tangle formation. There were no significant differences in individual thalamic nuclear [3H]-D-aspartate binding between controls and the AD and PD groups.
Neuropathol Appl Neurobiol 1990 Dec
PMID:Distribution of neurofibrillary tangle formation and [3H]-D-aspartate receptor binding in the thalamus in the normal elderly brain, in Alzheimer's disease and in Parkinson's disease. 196 33

Striatal dopamine D-1 receptor binding was investigated in vivo with positron emission tomography (PET) in five patients with early Parkinson's disease using [11C]-SCH 23390. All patients had predominantly unilateral symptoms and showed a significant reduction in the accumulation of [18F]-6-F-DOPA in the striatum contralateral to the symptoms. None of the patients had received any antiparkinsonian medication. The striatal and cerebellar radioactivity was measured and corresponding striatum/cerebellum ratios were counted. The mean striatum/cerebellum ratio of [11C]-SCH 23390 binding was symmetric between the hemispheres. By contrast, the striatum/cerebellum ratio of [11C]raclopride binding, labelling dopamine D-2 receptors, was increased significantly in the hemisphere contralateral to the symptoms as compared with the opposite hemisphere. Thus, the present results show that the behaviour of striatal D-1 and D-2 receptors is different in early Parkinson's disease.
J Neurosci Res 1990 Dec
PMID:PET demonstrates different behaviour of striatal dopamine D-1 and D-2 receptors in early Parkinson's disease. 198 15

Schwann cells from transected peripheral nerve segments are known to produce nerve growth factor (NGF). We performed adrenal medullary grafts or cografts of adrenal medulla and sciatic nerve into the striatum of MPTP-treated young adult mice, and compared the survivability of grafted chromaffin cells and the recovery of intrinsic host DA fibers using computerized image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers and neurochemical analysis with high performance liquid chromatography (HPLC). Adrenal medullary chromaffin cells cografted with sciatic nerve survived better than those in adrenal grafts alone; host DA fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. A large number of TH-IR surviving cells in cografted mice showed long neuronal processes which were rarely seen in the mice receiving adrenal graft alone. We conclude that cograft of adrenal medulla and sciatic nerve promotes intrinsic host DA fiber recovery better than adrenal medulla grafts alone, and that survivability of grafted chromaffin cell may promote host DA fiber recovery. Adrenal medullary autografts have been used in patients with Parkinson's disease; we suggest that if this approach is to be used in the future, methods to increase the survivability of grafted chromaffin cells, such as co-grafting with pieces of peripheral nerve, be considered to enhance the survivability of the chromaffin cells, which might be closely related to the functional recovery of the patients by this grafting procedure. Of course, such strategies as the present cografting approach must be demonstrated to work in older animals using older donor tissue before proceeding to this next step in humans.
Brain Res 1990 Dec 24
PMID:Cografts of adrenal medulla with peripheral nerve enhance the survivability of transplanted adrenal chromaffin cells and recovery of the host nigrostriatal dopaminergic system in MPTP-treated young adult mice. 198 43


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