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)

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

Graphite furnace atomic-absorption spectroscopy was used to measure aluminum concentrations in brain samples from 33 patients dying from a variety of neurologic diseases. Four samples from patients dying of nonneurologic causes also were studied. Nine samples (one from each of nine patients) of Creutzfeldt-Jakob disease brain contained normal amounts of aluminum. Aluminum was increased in 9 of 18 brain specimens with seven different pathologic processes. This included three of seven Alzheimer disease, two of three Huntington disease, two of two Parkinson disease, one of one progressive supranuclear palsy, one of one acoustic neuroma, one of two cerebrovascular disease, and one of two Guamanian amyotrophic lateral sclerosis (ALS). Aluminum was normal in the remaining samples (four normal, two ALS, one multiple sclerosis, one Pick disease, and two Guamanian parkinsonism-dementia). The significance of high aluminum values is not clear, but the normal values from the Creutzfeldt-Jakob cases imply that neuronal destruction per se need not lead to accumulation of aluminum in the brain.
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PMID:Brain destruction alone does not elevate brain aluminum. 645 8

We studied the relative etiologic importance upon the development of Parkinson's disease (PD) of occupational exposure to herbicides and other compounds, ionizing radiation exposure, family history of PD and essential tremor, smoking, and history of various viral and other medical conditions. We identified patients (n = 130) with neurologist-confirmed idiopathic PD through contacts with Calgary general hospitals, long-term care facilities, neurologists, the Movement Disorder Clinic, and the Parkinson's Society of Southern Alberta, and selected two matched (by sex and age +/- 2.5 years) community controls for each case by random digit dialing. We obtained lifetime work, chemical, radiation, medical, and smoking exposure histories and family histories of PD and essential tremor by personal interviews, and analyzed the data using conditional logistic regression for matched sets. After controlling for potential confounding and interaction between the exposure variables, using multivariate statistical methods, having a family history of PD was the strongest predictor of PD risk, followed by head trauma and then occupational herbicide use. Cases and controls did not differ in their previous exposures to smoking or ionizing radiation; family history of essential tremor; work-related contact with aluminum, carbon monoxide, cyanide, manganese, mercury, or mineral oils; or history of arteriosclerosis, chicken pox, encephalitis, hypertension, hypotension, measles, mumps, rubella, or Spanish flu. These results support the hypothesis of a multifactorial etiology for PD, probably involving genetic, environmental, trauma, and possibly other factors.
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PMID:Parkinson's disease: a test of the multifactorial etiologic hypothesis. 817 May 64

Neurons in the substantia nigra may be vulnerable to oxidant stress because (a) the metabolism of dopamine generates peroxides, which, in the presence of iron, can lead to the formation of the highly reactive hydroxyl free radical; and (b) neuromelanin within nigral neurons can bind metals such as iron and aluminum and thereby promote the site-specific formation of free radicals. Postmortem studies show increased iron, decreased glutathione, and increased lipid peroxidation in the substantia nigra of patients with Parkinson's disease (PD). Recent studies also report iron and aluminum accumulation within neuromelanin granules of patients with PD. These findings suggest that the substantia nigra in the patient with PD is in a state of oxidant stress and that antioxidant therapy might protect residual dopamine neurons and slow the natural progression of PD. Selective inhibitors of monoamine oxidase type B (MAO-B) have been chosen for study because of their capacity to interfere with the oxidative metabolism of dopamine and so diminish the likelihood that free radicals will be formed. Initial studies demonstrate that the MAO-B inhibitor L-deprenyl (selegiline) delays the development of disability in otherwise untreated patients with early Parkinson's disease. Although the mechanism responsible for these observations remains unclear, these results are consistent with the possibility that L-deprenyl provides neuroprotective effects.
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PMID:A rationale for monoamine oxidase inhibition as neuroprotective therapy for Parkinson's disease. 830 2

The presence of both aluminum (Al) and manganese (Mn) in central nervous system tissues (CNS) has been reported in Parkinson's disease and in parkinsonism-dementia (PD) on Guam. Epidemiological surveys on Guam have suggested that low calcium (Ca), magnesium (Mg) and high Al and Mn in river, soil and drinking water may be implicated in the pathogenesis of PD. Experimentally, low Ca-Mg diets with or without added Al have been found to accelerate Al deposition in the CNS of rats and monkeys. Although excessive deposition of Mn produces similar neurotoxic action to Al in CNS tissues, the mechanism of Mn deposition coupled with Al loading in the presence of low Ca-Mg intake is not yet known. In this study, the deposition and mental-metal interaction of both Al and Mn in the CNS, visceral organs and bones of rats fed unbalanced mineral diets were analyzed. Male Wistar rats, weighing 200 g, were maintained for 90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. Al and Mn content were determined in the frontal cortex, spinal cord, kidney, muscle, abdominal aorta, femur and lumbar spine using neutron activation analysis (NAA). Our results demonstrate that serum Ca levels were decreased in the following dietary order: C<D<B<A. Serum Mg levels were significantly lower in rats from Groups C and D, compared with those in Groups A and B, reflecting the content of Mg and other interacting minerals in the diet. There was no significant difference in serum Al, zinc and phosphorus levels. Ca and Mg contents in lumbar vertebrae and the femur were significantly lower and Al levels significantly higher in rats maintained on the low Ca-Mg diet with or without added Al. Al content in CNS tissues and visceral organs were highest in rats fed diets deficient in Ca alone or low in Ca-Mg with or without added Al. Bone Mn levels significantly increased in rats fed the low Ca-Mg diet with added Al. Mn content in the frontal cortex significantly increased in rats fed diets low in Ca-Mg with or without added Al. But the Mn content of other tissues including the spinal cord, kidney, muscle and abdominal aorta was unchanged in rats given Ca deficient diets. Intake of low Ca and Mg with added Al in rats led to the high concentrations of Mn and Al in bones and in the frontal cortex. We conclude that unbalanced mineral diets and metal-metal interactions may lead to the unequal distribution of Al and Mn in bones and ultimately in the CNS inducing CNS degeneration.
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PMID:Effects of calcium-deficient diets on manganese deposition in the central nervous system and bones of rats. 858 82

We gave three adult rhesus monkeys seven IV injections of manganese chloride at approximately 1-week intervals. We evaluated neurologic status by serial clinical examinations and performed a levodopa test if the animal developed features of basal ganglia dysfunction. After the animals were killed, we performed neuropathologic, neurochemical, and laser microprobe mass analysis (LAMMA) studies. Two of three animals developed a parkinsonian syndrome characterized by bradykinesia, rigidity, and facial grimacing suggestive of dystonia but not tremor. Neither animal responded to levodopa. Autopsy demonstrated gliosis primarily confined to the globus pallidus (GP) and the substantia nigra pars reticularis (SNr). We detected focal mineral deposits throughout the GP and SNr, particularly in a perivascular distribution. LAMMA studies noted that mineral deposits were primarily comprised of iron and aluminum. The severity of pathologic change correlated with the degree of clinical dysfunction. These studies demonstrate that, in contrast to Parkinson's disease (PD) and MPTP-induced parkinsonism, manganese primarily damages the GP and SNr and relatively spares the nigrostriatal dopaminergic system. Further, the results suggest that Mn-induced parkinsonism can be differentiated from PD and MPTP-induced parkinsonism by the clinical syndrome and response to levodopa. The accumulation of iron and aluminum suggests that iron/aluminum-induced oxidant stress may contribute to the damage associated with Mn toxicity.
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PMID:Manganese intoxication in the rhesus monkey: a clinical, imaging, pathologic, and biochemical study. 861 20

In susceptible species, aluminum induces cytoskeletal changes in which neurofilaments accumulate in neuronal cell bodies and proximal axonal enlargements. To determine if microtubule-associated proteins (MAPs) are altered in this model, we examined the spinal cords of aluminum- and saline-treated control rabbits at several time points after treatment. Transient decreases in tau and MAP2 immunoreactivity in neurons in aluminum-intoxicated rabbits were demonstrated with immunocytochemistry. An antibody directed against Alzheimer's disease paired helical filaments labeled neurons in aluminum-treated rabbits but not controls. MAP5 immunoreactivity in the cell body cytoplasm was displaced by aluminum-induced tangles. The transient decreases in MAP2 and tau immunoreactivity did not reflect alterations in protein levels measured using immunoblotting. The transient antigenic changes in tau and MAP2 may reflect conformational changes in these cytoskeletal proteins. Aluminum-induced pathology provides a model for studying perturbations in MAPs and neurofilament proteins that are characteristic of many human neurodegenerative diseases such as Alzheimer's disease, diffuse Lewy body disease, Parkinson's disease, and amyotrophic lateral sclerosis.
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PMID:Aluminum-induced neuropathology: transient changes in microtubule-associated proteins. 894 45

Aluminum is a neurotoxin and in susceptible species induces a neurofibrillary pathology characterized by argentophilic masses in neuronal perikarya and in axonal spheroids. These inclusions are known to contain neurofilament proteins. Using immunocytochemistry and immunoblotting, we demonstrate that tau is a component of these aluminum-induced neurofibrillary tangles (Al-NFTs) in rabbits. Double-label immunocytochemistry experiments reveal co-localization of phosphorylated neurofilaments (using SMI31) and tau (using tau-1, tau-5, AT8, and PHF-1) in the perikaryal Al-NFTs. Non-phosphorylated tau (detected using tau-1) occupies a smaller area of the Al-NFT than the total pool of tau proteins (detected using tau-5). The area of total tau and non-phosphorylated tau immunolabeling in the Al-NFT increases as the size of the Al-NFT (i.e., the proportion of cell area occupied by the Al-NFT) increases. The proportion of cell area (outside of the Al-NFT) occupied by tau (as indicated by tau-5) decreases as the area of tau in the Al-NFT increases and as the size of the Al-NFT in the cell increases. Immunoblotting experiments demonstrate 1) the specificity of the tau antibody labeling and verify a lack of cross-reactivity of the tau-5 antibody to neurofilament proteins in rabbit tissue; and 2) no alterations in the levels of tau resulting from aluminum-treatment. These data suggest that as the size of the Al-NFT in a cell increases there is less tau in the neuronal perikarya. Therefore, there may be less tau in the perikarya available to perform normal functions such as microtubule polymerization and stabilization. Tau and neurofilament proteins are perturbed in a number of neurodegenerative disorders such as Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease. Aluminum-induced neurofibrillary pathology may provide a model to study perturbation in tau and neurofilaments, their phosphorylation and deposition into pathological inclusions.
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PMID:Tau in aluminum-induced neurofibrillary tangles. 921 89

Alterations in cytoskeletal proteins such as the perikaryal accumulation of neurofilaments (NFs) occur in a number of human neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis and may contribute to their debilitating effects. The administration of aluminum salts to rabbits induces the aberrant accumulation of NFs within the proximal axons and perikarya of vulnerable neurons and is one animal model which has been extensively studied in an attempt to gain insight into the mechanism(s) of NF perturbations in human disease. Previous studies using Northern blotting techniques to examine mRNA levels in the aluminum-induced neuropathy model have led to seemingly contradictory results. We have used in situ hybridization which provides the cellular resolution needed to: 1) determine whether there are generalized decreases in the levels of mRNA expression or decreases in mRNA encoding specific proteins; 2) determine whether alterations in mRNA levels occur specifically in neurons with NF accumulations; and 3) begin to resolve some of the apparent contradictions in the literature. A moderate dose of aluminum lactate administered on two consecutive days produced neurofibrillary tangles in spinal cord neurons seven days after the first dose. Polyadenylated mRNA levels were not altered in spinal cord neurons in aluminum-treated compared to saline-treated control animals or in tangle-bearing compared to non tangle-bearing neurons in aluminum-treated animals. Middle and high NF subunit (NFH) mRNA levels were not significantly different from polyadenylated mRNA levels in spinal cord neurons in aluminum-treated/control animals. NFH mRNA levels were decreased in neurons containing aluminum-induced NF accumulations. These results suggest that NFH gene expression may be down regulated by an inhibitory feedback mechanism induced by perikaryal accumulations of NFs. This inhibitory feedback regulation for NFH may have implications for neurodegenerative diseases in which NFs accumulate in neuronal perikarya.
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PMID:Neuronal gene expression in aluminum-induced neurofibrillary pathology: an in situ hybridization study. 921 90

In a previous report, Alzheimer's disease risk factors, including alcohol abuse, depression, Down's syndrome, cerebral glucose metabolism defect, head trauma, old age, Parkinson's disease, sleep disturbance, and underactivity, were shown to have an association with reduced cerebral blood flow. In this report an attempt is made to strengthen a hypothesis that reduced cerebral blood flow may be a required cofactor in the cause of Alzheimer's disease with examples of additional putative risks, including aluminum, ApoE 4 alleles, estrogen deficiency, family history of dementia, low education-attainment, olfactory deficit, and underactivity coupled with gender, considered to have a relationship or potential relationship with reduced cerebral blood flow. Factors, believed to ameliorate Alzheimer's disease, associated with improved or stabilized cerebral blood flow are tabulated. A tentative cerebral blood flow nomogram is shown as a potential model to possibly help predict Alzheimer's disease susceptibility.
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PMID:Alzheimer's disease risk factors as related to cerebral blood flow: additional evidence. 948 78


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