Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to elucidate the effects of MPTP on enkephalinergic neurons, dopamine (DA), norepinephrine (NE), proenkephalin (PE) mRNA and met-enkephalin (ME) were measured in striatum, olfactory tubercle, and prefrontal cortex of C57/B16 mice 1 day-2 weeks following treatment with 96 mg/kg MPTP HCl (24 mg/kg i.p., twice/day for 2 days). DA and its metabolites were depleted 70% in striatum and 40% in olfactory tubercle within 1 day. In cortex, DA was unchanged, whereas homovanillic acid and NE were depleted 50 and 40% respectively by 3 days. ME increased in all three brain regions at different times whereas PE mRNA showed a different pattern in each region, with an increase in olfactory tubercle, a decrease in cortex, and in striatum, a decrease at 1 day followed by an increase at 3 days. Thus enkephalinergic neurons in each region respond differently to MPTP treatment. In striatum and olfactory tubercle. DA is depleted sufficiently to release its tonic inhibition on the enkephalinergic neurons, thereby leading to increased enkephalin synthesis. In cortex, the change in NE metabolism appears to cause a decrease of ME release and thereby a depression of PE synthesis. The possible relationship between these results and the changes observed in Parkinson's disease are discussed.
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PMID:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) effects on enkephalinergic neurons in various regions of mouse brain. 843 70

Olfactory dysfunction occurs in most patients with idiopathic Parkinson's disease (PD). In this study, we sought to determine whether such dysfunction is also present in progressive supranuclear palsy (PSP), a condition which shares a number of motor symptoms with PD and is commonly misdiagnosed as PD. We administered the University of Pennsylvania Smell Identification Test, a standardized test of odor identification ability, to 21 PSP patients; 17 also received a forced-choice odor detection threshold test. We compared the olfactory test scores to those obtained from PD patients and normal controls matched to the PSP patients on the basis of age, sex, and smoking habits. Overall, the olfactory function of the PSP patients was markedly superior to that of the PD patients and did not differ significantly from that of the normal controls. There was no association in either the PSP or PD patient groups between (1) the olfactory test scores and (2) measures of motor symptom severity, disease stage, and medication usage. These findings demonstrate that patients with PSP and PD differ markedly in their ability to smell and suggest that olfactory testing may be useful in their differential diagnosis.
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PMID:Olfactory testing differentiates between progressive supranuclear palsy and idiopathic Parkinson's disease. 849 53

We have recently reported that treatment of gonadectomized female and male C57/B1 mice with the gonadal steroid hormone, estrogen, reduced nigrostriatal dopaminergic neurotoxicity resulting from the Parkinson's-like inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the present report we examined whether the predominantly male gonadal steroid hormone, testosterone, would similarly modulate MPTP-induced neurotoxicity. Male C57/B1 mice were assigned to one of the following five treatment conditions: (1) Intact, (2) Orchidectomized, (3) Intact + MPTP, (4) Orchidectomized + Testosterone + MPTP and (5) Orchidectomized + MPTP. Corpus striatal and olfactory tubercle dopamine. DOPAC and norepinephrine concentrations were determined from the animals within each of the five treatment conditions. Orchidectomy alone failed to alter striatal dopamine and DOPAC concentrations, with levels obtained being similar to that of Intact animals. MPTP treatment significantly reduced striatal reduced striatal dopamine and DOPAC concentrations, regardless of hormonal condition of the animal. Similar results were obtained for olfactory tubercle determinations, with the exception that DOPAC levels from Orchidectomized mice were significantly greater than Intact males. No significant differences were obtained for norepinephrine within either brain area sampled. These results show that unlike estrogen, testosterone is devoid of any capacity to modulate nigrostriatal dopaminergic neurotoxicity resulting from MPTP. These findings may be related to the gender differences which exist in the prevalence of Parkinson's disease.
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PMID:Effects of testosterone upon MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system of C57/B1 mice. 873 29

Corticotropin-releasing factor (CRF) plays a major role in coordinating the endocrine, autonomic, behavioral and immune responses to stress through actions in the brain and the periphery. CRF receptors identified in brain, pituitary and spleen have comparable kinetic and pharmacological characteristics, guanine nucleotide sensitivity and adenylate cyclase-stimulating activity. Differences were observed in the molecular mass of the CRF receptor complex between the brain (58,000 Da) and the pituitary and spleen (75,000 Da), which appeared to be due to differential glycosylation of the receptor proteins. The recently cloned CRF receptor in the pituitary and the brain (designated as CRF1) encodes a 415 amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G-protein-coupled receptors. A second member of the CRF receptor family encoding a 411 amino acid rat brain protein with approximately 70% homology to CRF1 has recently been identified (designated as CRF2); there exists an additional splice variant of the CRF2 receptor with a different N-terminal domain encoding a protein of 431 amino acids. In autoradiographic studies, CRF receptors were localized in highest densities in the anterior and intermediate lobes of the pituitary gland, olfactory bulb, cerebral cortex, amygdala, cerebellum and the macrophage-enriched zones and red pulp regions of the spleen. CRF can modulate the number of CRF receptors in a reciprocal manner. For example, stress and adrenalectomy increase hypothalamic CRF secretion which, in turn, down-regulates CRF receptors in the anterior pituitary. CRF receptors in the brain and pituitary are also altered as a consequence of the development and aging processes. In addition to a physiological role for CRF in integrating the responses of the brain, endocrine and immune systems to physiological, psychological and immunological stimuli, recent clinical data implicate CRF in the etiology and pathophysiology of various endocrine, psychiatric, neurologic and inflammatory illnesses. Hypersecretion of CRF in the brain may contribute to the symptomatology seen in neuropsychiatric disorders, such as depression, anxiety-related disorders and anorexia nervosa. Furthermore, overproduction of CRF at peripheral inflammatory sites, such as synovial joints may contribute to autoimmune diseases such as rheumatoid arthritis. In contrast, deficits in brain CRF are apparent in neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, as they relate to dysfunction of CRF neurons in the brain areas affected in the particular disorder. Strategies directed at developing CRF-related agents may hold promise for novel therapies for the treatment of these various disorders.
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PMID:Corticotropin-releasing factor receptors: physiology, pharmacology, biochemistry and role in central nervous system and immune disorders. 883 89

Olfactory function impairment has been observed in patients with idiopathic Parkinson's disease (PD) using psychophysical procedures. In this study, an electrophysiological technique based on spectral analysis and topographic EEG mapping was used to evaluate EEG arousal response to olfactory stimulation in ten normal subjects and ten PD patients in stage II according to Hoehn and Yahr's scale, all of whom had akinetic-rigid syndrome and were receiving chronic L-Dopa therapy. Olfactory function was stimulated using diluted benzaldehyde by means of an apparatus set up in our laboratory. Spontaneous and post-olfactory stimulus EEGs were recorded from 20 electrodes placed upon the scalp according to the Int. 10-20 System. Total EEG power (from 0.5 to 19.5 Hz) was evaluated over 10 sec. artefact-free epochs. An olfactory arousal reaction was detected in nine of the ten PD patients and was characterised by a significant decrease in total power similar to that observed in all of the 10 normal subjects; these variations in EEG were found in all but the anterior regions of the scalp. The use of this technique does not seem to reveal any clear alteration in the olfactory function of PD patients.
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PMID:Evaluation of olfactory function by topographic EEG analysis in patients with Parkinson's disease. 883 85

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.
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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 aim of this investigation was to compare olfactory functions of patients suffering from Parkinson's disease (PD) and Alzheimer's disease (AD). Olfactory threshold, odor identification ability and odor memory performance were assessed in 21 non-demented PD patients and in 22 AD patients. Both patient groups were impaired in relation to an age-matched control group for the measure of odor identification. AD patients showed a higher olfactory threshold and poorer odor memory performance.
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PMID:Olfactory functions in Parkinson's disease and Alzheimer's disease. 905 90

Olfactory evoked potential (OEP) recordings were undertaken using amyl acetate stimulation in 20 patients with Parkinson's disease, nine patients with Alzheimer's disease, seven patients with olfactory dysfunction with no other neurological disorder, and 17 control subjects. In order to eliminate the somatosensory factor from the combined somatosensory and olfactory components produced by amyl acetate stimulation, we substracted the potentials using odorless air from those using amyl acetate. In normal subjects, three components were observed, the mean latencies of which were 309 +/- 46, 484 +/- 61 and 710 +/- 55 ms. In all subjects with anosmia (n = 7), no responses were observed. In the patients with Alzheimer's disease, the components were fewer despite having no olfactory dysfunction. In the 20 patients with Parkinson's disease, eight [corrected] patients showed no components, seven patients showed one component and four [corrected] patients showed two components. The components rarely were detected in spite of whether the patients had olfactory dysfunction or not. Olfactory evoked potentials are useful in detecting olfactory dysfunction and the early stages of Alzheimer's disease and Parkinson's disease.
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PMID:Olfactory evoked potentials in Parkinson's disease, Alzheimer's disease and anosmic patients. 920 69

For the past 40 years, research into Parkinson's disease (PD) has been predominantly the province of epidemiologists interested in pursuing the connection between the disease and environmental factors such as viral infection or neurotoxins. Hereditary influences were actually discounted because of a high monozygotic twin discordance rate found in studies that were later shown to be inadequate and inconclusive. There has recently been a resurgence of interest in investigating hereditary factors in PD when it became more and more apparent that a positive family history was a major risk factor for the disease. Meanwhile, it also became increasingly apparent from neuropathological studies that the common, idiopathic form of Parkinson's disease had, in fact, a pathological correlate, i.e., the existence of Lewy bodies, an eosinophilic cytoplasmic inclusion body, distributed diffusely throughout the substantia nigra, hypothalamus, hippocampus, autonomic ganglia and olfactory tracts. Although candidate gene approaches to linkage in PD families have not been rewarding, a genome wide scan mapped PD to 4q21-23 in one large family with PD with diffuse Lewy bodies, where a candidate gene, alpha-synuclein, resides. This gene encodes a presynaptic protein of which a peptide fragment is known to be a constituent of Alzheimer's disease plaques. The identification of a missense mutation in the alpha-synuclein gene in four independent PD families suggests that at least some fraction of familial PD with diffuse Lewy bodies is the result of an abnormal protein that interferes with normal protein degradation leading to the development of inclusions and ultimately neuronal cell death. There may be common pathogenetic mechanisms involved in alpha-synuclein mutations in PD and beta-amyloid and presenilin gene mutations in Alzheimer's disease.
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PMID:Genetics of Parkinson's disease. 930 Jun 60

Impaired olfactory function is commonly observed in idiopathic Parkinson's disease (IPD). However, it is unknown whether it is also found in familial parkinsonism. To address this issue we administered a smell test to 12 affected, three monosymptomatic, and 12 at-risk individuals from six large parkinsonian kindreds. Three kindreds exhibited an IPD phenotype and three exhibited a parkinsonism-plus syndrome (PPS) phenotype. All but one of the affected individuals had impaired olfactory function. In contrast, only five of the 12 at-risk individuals had impaired olfactory function. The degree of olfactory impairment in the at-risk individuals was less severe than in the affected individuals. The difference in the degree of olfactory impairment in individuals exhibiting the IPD and the PPS phenotypes was not statistically significant. These findings suggest that olfactory dysfunction is a phenotypic characteristic of familial parkinsonism and that it is independent of the kindred phenotype. The appearance of olfactory dysfunction soon after disease onset raises the possibility that it is part of the neurodegenerative disease process.
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PMID:Olfactory dysfunction in familial parkinsonism. 937 5


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