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 etiology of the nigrostriatal pathway degeneration in Parkinson's disease (PD) is unknown but there is a growing pool of evidence that environmental factors may be involved in the genesis of this disorder. The discovery of the N-Methyl 4-Phenyl 1,2,3,6-Tetrahydro-Pyridine (MPTP)-induced injury in late 1970s provided the first experimental model of PD and stimulated dramatically the epidemiological research. An excitotoxic amino acid contained in Cycadales, which is thought to be responsible for the amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam, provides another example of toxin-induced parkinsonism. This amino acid is present in most seeds common in the Western diet. In developed countries, prevalence of PD is 2 to 5 times as high than in developing countries. PD patients in developed countries are more likely than controls to have lived in rural environment. Case control studies have suggested that this positive association is possibly related to pesticides and herbicides exposures or well water drinking. Dietary surveys are now going on and several hypothesis are tested including high MPTP-structural analogs or seeds consumption in PD patients and low antioxidants consumption. The negative association between smoking habits and PD has been recognized for more than 20 years. There is evidence that this association is not an artefact due to the disease affecting smoking habits. Its origin is unknown but it could provide important aetiological clues for PD. The most recent hypothesis concerning the relationships between these environmental factors and PD are reviewed and pertinent suitable surveys for the future are discussed.
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PMID:[Parkinson's disease and environmental factors]. 175 3

We have studied a large family with familial amyotrophic lateral sclerosis (FALS) and examined the brain and spinal cord of a 40-year-old male family member at autopsy three years after clinical onset of the disease. The most unusual finding was a severe degree of neuronal loss of the substantia nigra accompanied by gliosis and numerous pigment-laden macrophages. There was marked degeneration of the upper and lower motor neurons and the corticospinal tracts. In addition, there was an unusually severe degree of diffuse degeneration throughout the anterolateral columns of the spinal cord. The posterior columns and Clarke's nucleus were not involved. Nigral degeneration has rarely been reported in FALS. The findings in this case emphasize the great variability of morphologic changes encountered in FALS and raise the question of a relationship between FALS and extrapyramidal disorders such as Parkinson's disease. We conclude that careful postmortem examinations of further cases of FALS are needed to fully define the extent of degenerative changes in this disease.
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PMID:Degeneration of the substantia nigra in familial amyotrophic lateral sclerosis. 176 52

Dendritic spheroid bodies (SBs) and Lewy bodies (LBs) were identified in comparable numbers in the substantia nigra pars compacta (SBC) of nine parkinsonian cases and one case of striatonigral degeneration but were not found in cases of Huntington's disease or neurologically normal controls. The immunohistochemical profile of the SBs in dystrophic dendrites of nigrostriatal dopaminergic neurons was remarkably similar to that of the LBs found within dendrites or free of the SNC neuropil. Both types of inclusions stained positively with antibodies to tyrosine hydroxylase, ubiquitin and microtubule-associated protein-2 (MAP2), and negatively for Tau-2, although they had different ultrastructural appearances. A few intracellular LBs were stained by antibodies to neurofilament proteins (NFs) 68, 160, and 200 kD, but dendritic SBs and extracellular LBs were not so stained. These data indicate that dendritic SBs and extracellular LBs may have a common molecular pathogenetic origin in Parkinson's disease. On the other hand, the SBs seen in the pars reticulata (SNR) and in the distal nigrostriatal axons even in control cases were generally stained by antibodies to NFs and ubiquitin but not to MAP2. This latter staining pattern in similar to that shown by SBs in the anterior horn in ALS and in the cerebellum of neurologically normal brains and is believed typical of axonal as opposed to dendritic SBs.
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PMID:Two types of spheroid bodies in the nigral neurons in Parkinson's disease. 191 62

We reviewed the medical records of 821 Olmsted County residents who had suffered head trauma with presumed brain injury between 1935 and 1974 and were more than 40 years old at the time of their last medical assessment. These patients were followed over 15,000 person-years for dementia and other degenerative neurologic diseases. The standardized morbidity ratio (SMR) for dementia was 1.06, and the SMR for dementia of the Alzheimer type was 1.00. These values are not significantly elevated and are inconsistent with studies that suggest that head trauma is a risk factor for Alzheimer's disease. In addition, the SMRs for parkinsonism (1.04), Parkinson's disease (0.94), and amyotrophic lateral sclerosis (1.05) were not significantly elevated, providing no evidence that head trauma is a risk factor for these disorders. However, these latter results are based on smaller total case numbers.
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PMID:Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. 192 95

The cerebrospinal fluid (CSF) is a specific ultrafiltrate of plasma, which surrounds the brain and spinal cord. The study of its proteins and their alteration may yield useful information on several neurological diseases. By using various electrophoretic separation techniques, several CSF proteins have been identified derived from plasma or from brain. Different one-dimensional methods, such as agarose gel electrophoresis and isoelectric focusing, are of similar value in identifying the non-specific oligoclonal bands, which are mainly helpful in the diagnosis of multiple sclerosis and other inflammatory diseases. Isoelectric focusing has a greater resolution than other one-dimensional methods, and it yields additional data about disease-associated proteins occurring in Alzheimer's disease, Huntington's chorea and amyotrophic lateral sclerosis. Silver-stained two-dimensional gels provide more information about the complex protein composition of CSF, particularly about proteins produced in the brain, such as apolipoprotein E and neuron-specific enolase. For the detection of oligoclonal antibodies, the investigation of protein changes revealed by Parkinson's disease, schizophrenia and Creutzfeldt-Jakob disease, and the analysis of CSF immune complexes, two-dimensional electrophoresis has a greater sensitivity.
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PMID:Analysis of cerebrospinal fluid proteins by electrophoresis. 193 90

Amino acids such as L-glutamate und L-aspartate are major excitatory neurotransmitters in the mammalian central nervous system (CNS) and potential neurotoxins (excitotoxins), which can destroy central neurons by excessive activation of respective receptors. In the last three decades evidence has accumulated that excitatory amino acids (EAA) are involved in many neurological diseases and that pharmacological intervention offers prospects of novel and more effective therapies. Three different receptor types for EAA have been identified, each being named by the selective agonist to which it is preferentially sensitive, i.e. N-methyl-D-aspartate- (NMDA), kainate- and quisqualate-receptors. In this review interest is focused primarily on the NMDA-receptor, whose structure has been subject of numerous electrophysiological and biochemical studies. Today, it is well established that the NMDA-receptor-ionophore complex has an agonist binding site for glutamate, NMDA and related EAAs which is coupled with an ion channel permeable to Na+, K+, Cl- and Ca2+. Four other binding sites for glycine, phencyclidine, Mg2+ and Zn2+ have been identified which can differentially modulate the function of the NMDA receptor. An additional polyamine binding site has recently been reported. Numerous studies on experimental animals demonstrate that modulators of NMDA-mediated neurotransmission may have antiepileptic, anxiolytic, muscle-relaxant and memory-enhancing effects. Particular interest has gained the possible neuroprotective efficacy of NMDA-receptor antagonists in neurological diseases such as hypoxia/ischemia, hypoglycemia, epilepsy and chronic neurodegenerative disorders (Huntington's, Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, and AIDS encephalopathy).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The N-methyl-D-aspartate receptor complex. Various sites of regulation and clinical consequences]. 197 26

Several degenerative diseases of the central nervous system are characterized by the presence of neuronal inclusions. One of these inclusions, neurofibrillary tangles in Alzheimer's disease, has been shown to contain ubiquitin that belongs to a group of proteins known as heat shock proteins. Subsequent studies revealed that ubiquitin is also associated with various neuronal inclusions including Lewy bodies, Pick bodies and hyaline inclusions. Very recently, ubiquitin has been found also to be associated with glial inclusions that are unique to multiple system atrophy. The close association of ubiquitin with varying cellular inclusions, together with its function in the proteolytic process, raised the hypothesis that ubiquitin may be involved in the degradation of abnormal proteins appearing in the damaged neurons and glial cells. In central nervous system, a group of heat shock proteins collectively known as HSP 70 is also present which is constitutive and/or inducible. Since HSP 70 has been suspected to play a crucial role degradation and repair of abnormal intracellular proteins, we hypothesized that HSP 70 may be associated with those inclusions, as the case with ubiquitin. To test this we performed immunohistochemical studies on brain tissues from patients with various neurodegenerative conditions by using specific polyclonal antibody to HSP 70. Brain tissues were obtained at autopsy from each three patients with Alzheimer's disease, Pick's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and multiple system atrophy. Tissues were fixed in buffered formalin and embedded in paraffin. Immunostaining was performed by the standard ABC method using diaminobenzidine as a chromogen. Sections were lightly stained with hematoxylin. Polyclonal antibodies were raised in rabbits against mouse HSP 70.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[HSP 70 is associated with abnormal cytoplasmic inclusions characteristic of neurodegenerative diseases]. 205 24

We elicited motor evoked potentials (MEPs) using transcortical magnetic stimulation in 150 control subjects aged 14 to 85 years and 275 patients with a variety of diseases. There were no significant side effects. Cortex-to-target muscle latencies measured 20.2 +/- 1.6 ms (thenar), 14.2 +/- 1.7 ms (extensor digitorum communis), 9.4 +/- 1.7 ms (biceps), and 27.2 +/- 2.9 ms (tibialis anterior). Central motor delay between the cortex and the C-7 and L-5 measured 6.7 +/- 1.2 ms and 13.1 +/- 3.8 ms, respectively. Mean spinal cord motor conduction velocity measured 65.4 m/s. MEP amplitude expressed as a percentage of the maximum M wave was never less than 20% of the M wave. A value of less than 10% is considered abnormal. MEP latency increases linearly with age and central motor delay is longer in older subjects. Compound muscle action potentials and absolute MEP amplitudes decreased linearly with age. In multiple sclerosis (MS), MEP latency and central delay were often very prolonged. The MEP was more sensitive than the SEP in MS. In amyotrophic lateral sclerosis, MEP latencies were only modestly prolonged; the characteristic abnormality was reduced amplitude. When pseudobulbar features predominated MEPs were often absent. The MEP was of normal latency in Parkinson's disease, but age-related amplitude was often increased. MEP latency and amplitude were normal in Huntington's disease. Abnormal MEPs persisted several months after stroke despite good functional recovery. The MEP could be used to advantage to demonstrate proximal conduction slowing and block in demyelinating neuropathies. In plexopathy, ability to elicit an MEP several days after onset of paresis was good evidence of neuronal continuity in motor fibers.
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PMID:AAEM minimonograph #35: Clinical experience with transcranial magnetic stimulation. 793 34

Neurofibrillary degeneration is an argyrophilic intraneuronal lesion found in several unrelated neurologic conditions. The relationship between different types of neurofibrillary tangles is investigated with two monoclonal antibodies raised against Alzheimer neurofibrillary tangles (anti-ANT). Using the peroxidase-antiperoxidase technique, the authors demonstrate that neurofibrillary tangles of progressive supranuclear palsy, containing 15-nm straight filaments, share an antigenic determinant with ANTs. Ultrastructural studies localize the antigenic determinant to filamentous elements in the parakarya. The determinant is not present in normal brain, aluminum-induced experimental tangles in the rabbit, Lewy bodies, Hirano bodies, or axonal filamentous inclusions of amyotrophic lateral sclerosis and giant axonal neuropathy. It is, however, present in ANTs regardless of the pathologic condition in which they are found, including Alzheimer's disease, Down's syndrome, and postencephalitic Parkinson's disease.
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PMID:Monoclonal antibodies to Alzheimer neurofibrillary tangles. 2. Demonstration of a common antigenic determinant between ANT and neurofibrillary degeneration in progressive supranuclear palsy. 241 Nov 43

Main monoamine metabolities of cerebrospinal fluid (CSF), i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), were measured in 74 patients with neurodegenerative diseases, in 30 normal control subjects and in 16 diseased control subjects without neurodegenerative diseases. The symptoms of patients were scored according to an original scale. It was suggested by statistical study including multiple regression analysis that there might be significant relationship between CSF-MHPG level and extrapyramidal symptoms, or autonomic symptoms, and between CSF-5-HIAA level and extrapyramidal, or cerebellar symptoms, and between CSF-HVA level and extrapyramidal, pyramidal, or cerebellar symptoms. It was also suggested that the severer the symptoms of patients with Parkinson's disease, Shy-Drager syndrome, or olivopontocerebellar atrophy became, the lower the levels of monoamine metabolities of CSF became. The activity of peripheral catecholamine metabolism might influence the CSF-MHPG level because of the significant positive correlations between CSF-MHPG level and urine noradrenaline or vanillylmandellic acid level. The level of MHPG was high in patients with severe amyotrophic lateral sclerosis or hereditary spinocerebellar degeneration possibly because of stress with respiratory dysfunction.
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PMID:Study on monoamine metabolite contents of cerebrospinal fluid in patients with neurodegenerative diseases. 243 50


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