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)

Sensory disturbances such as olfactory or visual dysfunctions are common in Parkinson's disease (PD). A possible relationship between distorted colour discrimination and the nigrostriatal dopamine deficit is still a matter of debate. We examined 31 de novo Parkinsonian patients with [123I]beta-CIT single photon emission tomography (SPECT). We used a single-head gamma-camera and calculated the binding ratio striatum/cerebellum (specific/nonspecific binding) of [123I]beta-CIT uptake. On the same day, we performed the Farnsworth-Munsell 100 Hue Test (FMT) in these patients and estimated the total error score, in order to investigate abnormalities of colour vision. Parkinsonian patients' total error score was higher compared with an age- and sex-matched control group (P = < 0.0001), whereas disability scores of the Hoehn and Yahr scale (P = 0.019, Spearman r = 0.419) and the Unified Parkinson's Disease Rating Scale (P = 0.039, Spearman r = 0.373) correlated with total error score. No significant association appeared between total error score (Spearman r = -0.119, P = 0.525) and [123I]P-CIT-SPECT ratio. Thus both total error scores of the FMT and [1231]beta-CIT-SPECT binding ratios have been found to reflect the severity of PD. However, only [123I]beta-CIT SPECT reflects degeneration of dopaminergic neurons of the basal ganglia, but does not reflect alterations of the visual system and/or extranigral lesions in PD. From our results, we speculate that FMT may be a valuable clinical method to measure extranigral lesions of the visual system in PD.
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PMID:Colour vision abnormalities do not correlate with dopaminergic nigrostriatal degeneration in Parkinson's disease. 977 65

One of the primary areas of investigation in the pathophysiology of Parkinson's disease (PD) is the loss of the dopamine-producing cells in the melanized neurons of the substantia nigra, believed to be caused by oxidative stress resulting from excessive free radical activity. The cuprozinc enzyme, superoxide dismutase (SODCu2Zn2), catalyzes the dismutation of superoxide anions to hydrogen peroxide plus oxygen, and is normally found in high concentrations in the substantia nigra where it protects neurons by scavenging free radicals. Zinc supplementation has been shown to significantly increase SODCu2Zn2 in vitro. A novel oral zinc tally test (ZTT) used in the assessment of zinc status was administered to 100 PD patients and 25 controls. Patients with PD showed a significantly decreased zinc status as compared to controls (p < 0.001). Significance was also established for 3 self-reported health-related variables thought to be related to zinc status: vision problems, olfactory loss, and taste loss (p < 0.05). Relative risks for patients with PD for these variables were 1.51, 1.56, and 1.33, respectively. Zinc status as measured by the ZTT is negatively correlated with PD status. PD status is positively correlated with self-reported vision problems, and olfactory and taste loss. Further study of the role of zinc in the development and treatment of PD is warranted.
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PMID:Evidence of functional zinc deficiency in Parkinson's disease. 1010 31

Olfactory dysfunction is a common symptom of Parkinson's disease (PD). It may manifest in the early stages of the disease and infrequently may even antedate the onset of motor symptoms. The cause of olfactory dysfunction in PD remains unknown. Pathological changes characteristic of PD (i.e., Lewy bodies) have been demonstrated in the olfactory bulb which contains a large population of dopaminergic neurons involved in olfactory information processing. Since dopaminergic drugs do not affect olfactory threshold in PD patients, it has been suggested that olfactory dysfunction in these patients is not dependent on dopamine deficiency. I present two fully medicated Parkinsonian patients with long standing history of olfactory dysfunction in whom recovery of smell occurred during therapeutic transcranial application of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density. In both patients improvement of smell during administration of EMFs occurred in conjunction with recurrent episodes of yawning. The temporal association between recovery of smell and yawning behavior is remarkable since yawning is mediated by activation of a subpopulation of striatal and limbic postsynaptic dopamine D2 receptors induced by increased synaptic dopamine release. A high density of dopamine D2 receptors is present in the olfactory bulb and tract. Degeneration of olfactory dopaminergic neurons may lead to upregulation (i.e., supersensitivity) of postsynaptic dopamine D2 receptors. Presumably, small amounts of dopamine released into the synapses of the olfactory bulb during magnetic stimulation may cause activation of these supersensitive receptors resulting in enhanced sense of smell. Interestingly, in both patients enhancement of smell perception occurred only during administration of EMFs of 7 Hz frequency implying that the release of dopamine and activation of dopamine D2 receptors in the olfactory bulb was partly frequency dependent. In fact, weak magnetic fields have been found to cause interaction with biological systems only within narrow frequency ranges (i.e., frequency windows) and the existence of such frequency ranges has been explained on the basis of the cyclotron resonance model.
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PMID:Treatment with AC pulsed electromagnetic fields improves olfactory function in Parkinson's disease. 1037 49

Growth factors are believed to be involved in the mitotic regulation of the animal olfactory epithelium (OE). We investigated mucus covering the human OE area to see if it contained the insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) and to examine their behaviour in neurodegenerative diseases. Thirty patients with idiopathic late onset cerebellar ataxia (ILOCA), Parkinson's disease, and amyotrophic lateral sclerosis (ALS) and 30 age- and sex-matched healthy subjects were studied. In 10 controls, we also analyzed the mucus of the respiratory mucosa of the nose and tears. We detected IGF-I in the mucus covering the OE and Western ligand blot analysis (WLB) showed IGFBPs with an apparent Mr of 41, 500/38,500, 34,000 and 24,000, which were immunoprecipitated by specific antisera to IGFBP-3, -2 and -4, respectively. Their levels were higher than those observed in the respiratory mucosa of the nose or in tears. Mucus of the OE of the patients contained significantly reduced levels of IGF-I in comparison with those of controls. The intensity of all the IGFBPs-related bands were reduced in the ILOCA, while the remaining patients had a loss in the amounts of IGFBP-3. Plasma IGF-I and IGFBPs levels were similar in patients and controls. In conclusion, our data show that mucus covering the human OE contains IGF-I and IGFBPs, suggesting that these factors have a role in the activity of the OE. The amounts are reduced in the patients' mucus, possibly reflecting a dysfunction of the OE itself.
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PMID:Mucus of the human olfactory epithelium contains the insulin-like growth factor-I system which is altered in some neurodegenerative diseases. 1041 87

Nurr1, a member of the nuclear receptor superfamily of transcription factors, has been found to be essential for the development of ventral midbrain dopamine (DA)ergic neurons. To study the regional selectivity and phenotypic specificity of regulation by Nurr1 of the genesis of DAergic neurons, we examined DAergic, serotonin (5-HT)ergic, norepinephrine (NE)ergic, cholinergic, glutamate (GLU)ergic, and gamma-aminobutyric acid (GABA)ergic neurons in the brains of Nurr1-deficient mice by immunohistochemistry and biochemistry. We demonstrated that in homozygous Nurr1-deficient mice (Nurr1-/-), DAergic neurons were totally absent in substantia nigra and ventral tegmental area, but preserved in other regions including diencephalon and hypothalamus, olfactory bulb (OB). Levels of DA in Nurr1-/- mice were decreased by 98% in striatum (Str) and 65% in OB. NEergic neurons in locus ceruleus, 5-HTergic neurons in raphe nuclei, and cholinergic neurons in basal forebrain and other regions were not changed. A 30% reduction of NE was found in the Str of Nurr1-/- mice. The levels of GLU and GABA and the activity of choline acetyl transferase in the brains of Nurr1-/- mice were not significantly altered. Our results demonstrate a selective and specific deficit of DA and absence of DAergic neurons in the mesencephalic structures of Nurr1-deficient mice, which resembles the pattern similar to that seen in patients with Parkinson's disease (PD). This model may contribute to our understanding of the mechanisms influencing DAergic cell survival in PD.
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PMID:Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice. 1050 16

Recent advances in molecular biology, biochemistry, cell biology and behavioral pharmacology together with the development of more selective ligands to the various adenosine receptors have increased our understanding of the functioning of central adenosine A(2A) receptors. The A(2A) receptor is one of four adenosine receptors found in the brain. Its expression is highest in striatum, nucleus accumbens and olfactory tubercles, although it also occurs in neurons and microglia in most other brain regions. The receptor has seven transmembrane domains and couples via Gs to adenyl cyclase stimulation. Antagonistic interactions between A(2A) receptors and dopamine D(2) receptors have been described, as stimulation of the A(2A) receptor leads to a reduction in the affinity of D(2) receptors for D(2) receptor agonists. The A(2A) receptor is thought to play a role in a number of physiological responses and pathological conditions. Indeed, A(2A) receptor antagonists may be useful for the treatment of acute and chronic neurodegenerative disorders such as cerebral ischemia or Parkinson's disease. A(2A) receptor agonists may treat certain types of seizures or sleep disorders. This review discusses the characteristics, distribution, pharmacochemical properties and regulation of central A(2A) receptors, as well as A(2A) receptor-mediated behavioural responses and their potential role in various neuropsychiatric disorders.
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PMID:Central adenosine A(2A) receptors: an overview. 1061 96

A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown, alpha-synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for alpha-, beta-, and gamma-synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. Although antibodies to alpha- and beta-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. More significantly, we show here for the first time that alpha-, beta-, and gamma-synucleins are differentially expressed in cells of the OE and respiratory epithelium and that alpha-synuclein is the most abundant synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. Moreover, alpha- and gamma-synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. Thus, our data on synuclein expression within the OE may signify that synuclein plays a role in the regeneration and plasticity of ORNs in the adult human OE.
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PMID:The expression of alpha-, beta-, and gamma-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases. 1061 69

It has been known for over 30 years that olfactory function is disordered in idiopathic Parkinson's disease (IPD). The severity and partial specificity of anosmia was not realized until recently, with the advent of more detailed analysis and sophisticated measurement. The olfactory vector hypothesis suggests that the causative agent for IPD enters the brain via the nasal route, but the reason for olfactory dysfunction may be more subtle. Evidence for olfactory disturbance is reviewed from pathological, psychological, neurophysiological and genetic stand-points. It is proposed that the initial causative event in IPD may start in the rhinencephalon (olfactory brain) prior to damage in the basal ganglia.
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PMID:Is Parkinson's disease a primary olfactory disorder? 1062 64

Oxidant stress has been implicated in the pathogenesis of Parkinson's disease. To test the oxidant stress hypothesis of dopaminergic degeneration, age-related changes in the mesostriatal dopamine neuron system were compared between zitter mutant rats which have abnormal metabolism of oxygen species in the brain and Sprague-Dawley rat as a control using the neurochemistry and immunohistochemistry. Dopamine content in the caudate-putamen, nucleus accumbens and olfactory tubercle of zitter rats decreased significantly with age, and was lower than that found in corresponding age-matched controls. In the zitter rats, the reduction of dopamine was more prominent in the caudate-putamen than in the nucleus accumbens and olfactory tubercle. A characteristic decline of tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen of the zitter rat was also observed. In the dorsolateral caudate-putamen, reduction of tyrosine hydroxylase-immunoreactive fibers was observed in the matrix-like area, whereas in the ventromedial caudate-putamen the reduction occurred in the patch-like areas. Degeneration of tyrosine hydroxylase-immunoreactive fibers which was characterized by swollen varicosities and clustered fibers was observed in the caudate-putamen and nucleus accumbens and preceded loss of normal tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen. Thus, the depletion of dopamine in the terminal areas is related to axonal degeneration. However, there was no degenerative tyrosine hydroxylase-immunoreactive fibers in the olfactory tubercle at any examined age, but reductions of tyrosine hydroxylase-immunoreactive fibers and dopamine contents were noted in the olfactory tubercle after four months-of-age. Since the zitter rats have an abnormal oxygen metabolism, the degeneration of tyrosine hydroxylase-immunoreactive fibers could result from an accumulation of superoxide species. The present results provide support for the oxidant stress hypothesis of dopaminergic neuronal degeneration and further indicate the region-specific vulnerability of the nigrostriatal dopamine system.
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PMID:Age-related dopamine deficiency in the mesostriatal dopamine system of zitter mutant rats: regional fiber vulnerability in the striatum and the olfactory tubercle. 1065 18

The localization of glial cell line-derived neurotrophic factor (GDNF) family receptor alpha-1 (GFRalpha-1) was investigated in rat brain by immunohistochemistry using a polyclonal antibody against a specific sequence of the rat protein. For raising the antisera in rabbits, we synthesized the oligopeptide SDVFQQVEHISKGN that corresponds to residues 139 to 152 of rat GFRalpha-1. On immunospot assay, 0.5 microg/ml of an affinity-purified antibody was capable of detecting 7.8 pmol of the rat GFRalpha-1 oligopeptides. When rat brain homogenates were examined by Western blots, the antibody revealed two main bands with molecular weights of approximately 47 kDa and 53 kDa, corresponding to the known sizes of GFRalpha-1. Immunohistochemistry in rat brain demonstrated that GFRalpha-1-like immunoreactivity was present in neurons but not in glial cells. The localization of GFRalpha-1-like immunoreactivity was largely consistent with that of the corresponding GFRalpha-1 mRNA. Positive neurons were distributed widely in various brain regions, but were particularly abundant in such regions as the olfactory bulb, diagonal band, substantia innominata, zona incerta, substantia nigra, cerebellar cortex, nuclei of the cranial nerves including auditory system and spinal motoneurons. The present study showed that GFRalpha-1 in the normal central nervous system is expressed preferentially in certain multiple neuronal systems that include cholinergic system as well as dopaminergic system and motor neurons. As GFRalpha-1 protein was found in numerous brain structures, GDNF family ligands may have therapeutic application not only in degenerative diseases affecting in specific nervous systems, such as Parkinson's disease, amyotrophic lateral sclerosis and multiple system atrophy, but in diffusely damaging diseases like cerebrovascular diseases.
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PMID:Immunohistochemical localization of glial cell line-derived neurotrophic factor family receptor alpha-1 in the rat brain: confirmation of expression in various neuronal systems. 1072 Jun 15


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