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)

This paper reviews the changes in dopaminergic, cholinergic and glutamatergic neurotransmission, which occur in the aging of the central nervous system (CNS) and in age-related diseases: Parkinson's disease (PD) and Alzheimer's disease (AD). Dopaminergic neurotransmission is impaired with age due to degeneration of the substantia nigra pars compacta neurons and reduction of the density of postsynaptic D1 and D2 dopamine receptors in the striatum. PD is believed to be caused by a severe loss of dopaminergic neurons, which leads to nearly complete depletion of dopamine in the striatum, particularly in the putamen. The supersensitivity of postsynaptic dopamine receptors, reported by some authors, may result from compensatory mechanisms to degeneration of dopaminergic neurons. The role of aging in PD is also discussed in the paper. An interest in the role of the cholinergic and glutamatergic systems in aging results from the concept that the development of AD is due to the pathology of these systems. The data on cholinergic neurotransmission are controversial and imply that aging affects rather slightly both neurons and cholinergic receptors. In AD, however, severe degeneration of cholinergic neurons of the basal nucleus of Meynert, leading to the impairment of cholinergic neurotransmission in the hippocampus and the cerebral cortex, has been observed. In AD degeneration of glutamatergic neurons and subsensitivity of some excitatory amino acids receptors in the hippocampus and the cerebral cortex may lead to dementia. However, an increase in the glutamate release from presynaptic glutamatergic terminals may be responsible for neuronal degeneration in AD. The role of the beta-amyloid protein in a neurodegenerative activity of glutamic acid is discussed.
Pol J Pharmacol
PMID:Disturbances in neurotransmission processes in aging and age-related diseases. 840 65

T cells with gamma delta receptor form small percentage of lymphocytes in healthy individuals, whereas their number increases in persons with immunological disorders. Heat shock proteins (HSPs), which play a central role in protein transformation, could be antigens for gamma delta T cells. HSPs participate in mutual interactions of gamma delta cells and tissue cells, taking part in defense mechanism against infection and auto destruction. There is an interest' in the HSPs' role in modulation of both normal and pathological activity within the nervous system. HSPs can protect cells against undesired stimulation, probably by long-term protein expression. Results of the studies suggest participation of gamma delta T cells and HSPs in pathogenesis of certain diseases, including neurological ones (multiple sclerosis, Alzheimer's disease, Parkinson's disease and cerebrovascular diseases), although detailed explanation of this problem requires further studies.
Neurol Neurochir Pol
PMID:[Role of gamma-delta T-cells and heat shock proteins in immunological response and in pathogenesis of neurological diseases]. 858

The aim of the review is a brief description of the present status of research and perspectives in the field of multiple dopamine receptors, as well as of the importance of new discoveries for the treatment of schizophrenic psychoses and Parkinson's disease. Since the discovery of D1 and D2 dopamine receptors in the seventhies, evidence has accumulated for the existence of some new dopamine receptors. Among them the D3, D4 and D5 receptors, as well as their isoforms have been cloned. Molecular biology and pharmacology of these receptors have been exhaustively studied in recent years. These studies have prompted a number of hypotheses which open new perspectives for investigation into pathophysiology and therapy of schizophrenia and Parkinson's disease.
Pol J Pharmacol
PMID:Dopamine receptors--the present state of research and perspectives. 871 54

The qualitative changes in substantia nigra were analysed in the material of 25 cases of Parkinson's disease. A morphometric quantitative study of depletion of pigmented dopaminergic cells of substantia nigra was performed in six long-term cases of the disease. In addition, the number of melanin nodules was assessed as a marker of cell disintegration. The results obtained were compared with the morphometric evaluation of neuronal depletion in the mesocorticolimbic system (ventral tegmental area-VTA). The qualitative study indicated that melanin depletion in dopaminergic cells of substantia nigra in Parkinson's disease is diffuse and it is located mainly in the lateral alfa layer. Neuronal depletion with concomitant numerous extracellular neuromelanin nodules and granules was observed. A slight astrocytic gliosis free of macrophages accompanied cellular changes. The qualitative changes in substantia nigra are similar to those observed in VTA. The morphometric evaluation revealed that depletion of dopaminergic neurons in substantia nigra in Parkinson's disease is 73%, on average, while in VTA it remains under 5%. Hence, depletion in substantia nigra is much more intense. The analysis of the relationship between the number of neurons in substantia nigra and the age of subjects in the control group indicated that the number of neurons decreased proportionally to the age. In the group under study no significant relationship between neurons depletion and duration of disease or patients age was found. In the studied group of patients with Parkinson's disease, the number of melanin nodules in substantia nigra was significantly higher than in controls.
Neurol Neurochir Pol
PMID:[Morphometric assessment of lesions in the dopaminergic nigrostriatal system in Parkinson disease]. 914 73

In three neurological centres the therapeutic effects and adverse effects were compared of two levodopa preparations combined with carbidopa (25/250): 1. A foreign drug widely prescribed in Poland, and 2. Its Polish analogue produced by Polfa Stargard Works. The drugs were given to 30 patients (in two matched groups) with Parkinson disease or syndrome during 6 weeks. The trial was completed by 28 patients (one patient dropped out from each group for reasons not directly connected with the treatment). The therapeutic results were assessed on the basis of effects obtained in the NUDS and NSP scales and by measuring of the "on" phase at the beginning and at the end of the trial. In every case the global assessment of patient's condition by the patient and by the doctor was considered. The analysis of the results showed no significant statistically differences between both drugs respect to antiparkinsonian action and incidence of adverse effects.
Neurol Neurochir Pol
PMID:[Clinical trial of the first Polish levodopa preparation in the treatment of Parkinsonian patients]. 914 72

In 30 patients with Parkinson's disease (PD) CT scan, isotopic cisternography and neuropsychological examination were performed to test possible relationship between cerebrospinal fluid (CSF) turnover, intellectual impairment and brain atrophy. Pathological cisternography was found in one third of the patients and it was positively correlated with the Columbia Rating Scale. Cerebral atrophy on CT was found more frequently in patients with earlier onset of PD. Combined pathological pattern on CT scan and on cisternography was correlated with intellectual decline. We conclude from this study, that in PD intellectual deterioration and brain atrophy separately are not connected with abnormal CSF turnover.
Mater Med Pol
PMID:A cerebrospinal fluid turnover in Parkinson's disease. 916 16

Current views on the pathogenesis of Parkinson's disease are presented. Studies, particularly those carried out during the last decade, highlight the significance of endogenic processes responsible for a cumulative production of neurotoxic substances, especially free oxygen radicals which exert chronic effect on neurons. In Parkinson's disease, overproduction of free radicals and concomitant failure of protective mechanisms are most likely. An excess of free radicals is cytotoxic because of their very high chemical activity and uncontrolled chain reactions with numerous organic compounds, especially those which are mostly responsible for vital functions of cells. Oxidative stress disturbs metabolism of the cell what finally leads to its death most probably due to damage of cell membrane. That results in increased plasma membrane permeability for calcium ions which activate several subcellular mechanisms and initiate the final phase of cell death. Nonprotein-bound "free" iron ions are the strongest and most dangerous generators of free oxygen radicals. It is thought that ferric (Fe-3+" iron bound to neuromelanin may play a profound role in the overproduction of especially cytotoxic hydroxyl radicals, derivatives of molecular oxygen. Both, oxygen stress inducing factor and the sequence of related biochemical disorders remain still unknown. However, the synergy of the excess of reactive oxygen metabolites (mainly free radicals), nitric oxide, "free" iron ions and neuromelanin may contribute considerably to the generation of oxygen stress.
Neurol Neurochir Pol
PMID:[Current views on the mechanisms of dopaminergic neuron death of the nigrostriatal system in Parkinson's disease]. 938 Feb 59

This review deals with the new generation of selective and partly reversible monoamine oxidase (MAO) inhibitors. In contrast to the non selective inhibitors, used in the year 1957-1970, the selective inhibitors bind to and block only one of the two isoenzymes, MAO-A or MAO-B. The MAO-A inhibitors and part of the MAO-B inhibitors differ also from the classic drugs by their reversibility. The inhibition of MAO-A cause the rise of norepinephrine, dopamine and serotonin in the synaptic cleft, of MAO-B only of dopamine. The new inhibitors diminish also to some extent the reuptake of monoamines. The molecular action mechanism of the new drug generation is the same as in the non-selective drugs: increase of monoamines, near to the receptor, leads, after a number of intermediate steps, to activation of functional proteins in the cell. The selective block of one of the isoenzymes does not stop the metabolism of tyramine (from cheese, red wine), because this toxic compound is metabolised by both isoenzymes. The control of therapy with MAO-A inhibitors is easier, because of their reversibility. Selective inhibitors of MAO have found a secure place in therapy of depression (inh. of MAO-A, esp. Moclobemide) and Parkinson's disease (inh. of MAO-B, at this time mainly selegiline). Discussed is possible use of selective MAO-inhibitors for achieving an increase in cognitive function and protections of neurone cells from biochemical lesions.
Pol Merkur Lekarski 1997 Jul
PMID:[Inhibitory monoamine oxidases of the new generation]. 943 89

In the review paper is discussed the group of dopamine agonists which act directly on the postsynaptic receptors in the striatum, and have been used since over 20 years in the treatment of various stages of Parkinson's disease. For practical reasons they are divided in the paper into three groups: drugs used formerly and now gradually withdrawn mainly because of various adverse effects, new drugs whose effectiveness and usefulness have not yet been confirmed clinically, and three drugs (bromocriptine, lisuride, pergolide) used fairly widely with clinically confirmed effectiveness. The mechanism of their action and clinical results are described.
Neurol Neurochir Pol
PMID:[Dopamine agonist in the treatment of Parkinson's disease]. 944 45

Salsolinol is one of the dopamine-derived tetrahydroisoquinolines, supposed to be a potent dopaminergic neurotoxin, similar to MPTP. Its systemic administration induced parkinsonism in monkeys. The aim of the study was to compare the concentration of salsolinol and the metabolite of L-dopa, 3-O-MD, and the metabolite of dopamine, HVA, in the cerebrospinal fluid of patients with different degrees of parkinsonism, treated or nontreated with l-dopa. Lumbar CSF was obtained from 26 patients with Parkinson's disease (15 early and 11 advanced parkinsonism) and from six healthy controls. The presence of salsolinol, HVA and 3-O-MD was assayed with a sensitive HPLC method employing C18 (Hypersil BDS) column. The analysis of the results demonstrated that the concentration of salsolinol was related to the degree of parkinsonism but not affected by l-dopa treatment. In contrast, HVA and 3-O-MD were significantly elevated in patients receiving l-dopa but did not correlate with the severity of parkinsonism. The results suggest that salsolinol in the cerebrospinal fluid does not originate from exogenous l-dopa and its elevation in cerebrospinal fluid may be an indicator of the advancement of parkinsonism.
Neurol Neurochir Pol
PMID:[Salsolinol, 3-O-methyl-dopa and homovanillic acid in the cerebrospinal fluid of Parkinson patients]. 951 52


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