Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current epidemiological surveys in the Western Pacific area and Kii Peninsula have suggested that low calcium (Ca), magnesium (Mg) and high aluminum (Al) and manganese (Mn) in river, soil and drinking water may be implicated in the pathogenetic process of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD). The condition of unbalanced minerals was experimentally mimicked in this study using rats. 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. In the groups maintained on unbalanced mineral diets, calcium and magnesium contents of the bones were lower than those fed with standard diet. On the other hand, Ca content of CNS showed higher values in the unbalanced diet groups (especially in spinal cord of the low Ca-Mg plus high Al diet group) than those in the standard diet group. This was determined by neutron activation analysis (NAA) at Research Reactor Institute, Kyoto University. Also, Ca content in soft tissues of rats given unbalanced mineral diets was higher than those on standard diet. Mg content of soft tissues and spinal cord of rats was markedly lower in the low Ca-Mg plus high Al diet group than the other three groups as determined by inductively coupled plasma emission spectrometry (ICP). Six Kii cases with amyotrophic lateral sclerosis (ALS) also showed higher Ca and lower Mg contents in the CNS tissues than those of neurologically normal controls. As of today, calcification of the spinal ligaments (CSL) has been reported in only 120 cases in the world and 28 cases of CSL in the Kii Peninsula have been found in the same foci as ALS. We analyzed Mg content of 7 spinal bones and 10 ligaments of the CSL and Ca content of 5 spinal bones compared with controls. The CSL showed lower values of Mg contents in bones and ligaments compared to controls. The Ca content in bones of CSL was significantly lower than that of controls. These results suggest that the environmental factor may contribute to the pathogenesis of CSL due to low Ca and Mg intake as well as for ALS.
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PMID:[Similarities in calcium and magnesium metabolism between amyotrophic lateral sclerosis and calcification of the spinal cord in the Kii Peninsula ALS focus]. 928 69

Current epidemiological investigations in the Western Pacific including the Kii Peninsula of Japan, have suggested that environmental factors contribute to the pathogenetic process of amyotrophic lateral sclerosis (ALS) and parkinsonism dementia (PD). The condition of unbalanced minerals (a low content of calcium and magnesium, and a high content of aluminum) found in soil and drinking water in all three ALS foci was experimentally mimicked in our studies using rats. In rat groups maintained on unbalanced mineral diets, the calcium and magnesium contents of bones were lower than those fed a standard diet. In addition, the calcium content of CNS tissues showed higher values in the unbalanced diet groups (especially in the spinal cord of the low calcium and magnesium plus high aluminum diet group) than those in the standard diet group. The calcium content of other soft tissues as well as the CNS of rats fed unbalanced mineral diets was also higher than those on the standard diet. The magnesium content of soft tissues and spinal cord of rats was markedly lower in the low calcium and magnesium plus high aluminum diet group than in the other groups. Examination of tissues from six Kii Peninsula patients with ALS showed an average magnesium concentration in 26 CNS regions (cortical gray matter, white matter, basal ganglia, brain stem, spinal cord) significantly lower than that for five neurologically normal controls. The average calcium concentration in gray matter of ALS cases was significantly higher than that of controls. Interestingly, only 120 cases of calcification of spinal ligaments have been reported worldwide, and of these, 26 of 28 cases of calcification of spinal in the Kii Peninsula have been found to overlap the same geographic focal region as ALS. We analyzed the magnesium content of seven spinal vertebrae and 10 spinal ligaments of patients with calcification of spinal ligaments and the calcium content of five spinal bones compared with controls. The calcification of spinal ligaments patients had lower values for magnesium contents of bones and ligaments compared to controls and the calcium content of bones in these patients was significantly lower than that of controls. These data suggest that low dietary intake of calcium and magnesium over an extended period of time may contribute to the pathogenesis of patients with ALS and calcification of spinal ligaments.
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PMID:Effects of low calcium and magnesium dietary intake on the central nervous system tissues of rats and calcium-magnesium related disorders in the amyotrophic lateral sclerosis focus in the Kii Peninsula of Japan. 933 37

Aluminum is a neurotoxic metal that may be involved in the progression of neurodegenerative diseases, including Alzheimer disease and amyotrophic lateral sclerosis (ALS). Although the mechanism of action is not known, aluminum has been shown to alter Ca2+ flux and homeostasis, and facilitate peroxidation of membrane lipids. Since abnormal increases of intracellular Ca2+ and oxygen free radicals have both been implicated in pathways leading to neurodegeneration, we examined the effect of aluminum on these parameters in vitro using primary cultures of cerebellar granule cells. Exposure to glutamate (1-300 microM) caused a concentration-dependent uptake of 45Ca in granule cells to a maximum of 280% of basal. Pretreatment with AlCl3 (1-1000 microM) had no effect on 45Ca accumulation, but increased the uptake induced by glutamate. Similarly, AlCl3 had no effect on intracellular free Ca2+ levels measured using fluorescent probe fura-2, but potentiated the increase induced by glutamate. The production of reactive oxygen species (ROS) was examined using the fluorescent probe dichlorofluorescin. By itself, AlCl3 had little effect on ROS production. However, AlCl3 pretreatment potentiated the ROS production induced by 50 microM Fe2+. These results suggest that aluminum may facilitate increases in intracellular Ca2+ and ROS, and potentially contribute to neurotoxicity induced by other neurotoxicants.
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PMID:Aluminum potentiates glutamate-induced calcium accumulation and iron-induced oxygen free radical formation in primary neuronal cultures. 943 57

Age-related human neurodegenerative diseases are a major social and medical problem. It is therefore logical to take into consideration every theory with an overall approach to neurodegenerative diseases. This environmental proposal relies mainly on data concerning the Western Pacific amyotrophic lateral sclerosis-Parkinsonism-dementia complex (WP ALS-PD) considered as 'a prototypal human neurodegenerative disease' and on extrapolation from it to the bulk of neurodegenerative diseases (NDD). NDD would be due to an accelerated ageing process in certain populations of neurons due to the noxious synergy of (1) increased environmental slow deleterious factors (such as slow toxins) and of (2) decreased environmental protective factors (Mg deficient intake particularly). First, it was observed that three apparently dissimilar conditions occurred at extraordinary high rates in the Guam area: motoneuron disease (ALS), Parkinson's disease (P) and Alzheimer's-like dementia (D). Next, several other foci of endemic ALS-PD were found in Asia and Oceania in three Western Pacific population groups. These included the Chamorro people in Mariana Islands (Guam and Rota), the Auyu and Jakai people of West New Guinea and the Japanese residents of the Kii peninsula (Honshu island). The post-Second World War decline of the occurrence of WP ALS-PD in all three high incidence disease foci coupled with the absence of demonstrable heritable or transmissible factors had led to focus the search for the cause of this degenerative disease on nontransmissible environmental factors that are disappearing as the susceptible population groups acculturate to modern way. Epidemiologic study has shown that preference for traditional Chamorro food is the only one of 23 tested variables significantly associated with an increased risk for PD. An early suggestion incriminated the toxic seed of the false sago palm (Cycas circinalis L) which was used in traditional food and medicine. Laboratory investigation of cycad seed revealed the presence of various toxins and particularly of an 'unusual' non protein aminoacid: L-BMAA (beta-N-methylamino-L-alanine), an excitotoxic aminoacid. This slow toxin presents some structural similarity to another 'unusual' excitotoxic aminoacid: L-BOAA (beta-N-oxalyl-amino-L-alanine), an exogenous neurotoxin present in the grass pea (Lathyrus sativus) whose excessive consumption may cause lathyrism. The excitotoxicity of both L-BMAA and L-BOAA mainly concerns non-NMDA receptors. The neurotoxicity of these aminoacids varies with experimental models failing to induce an experimental model akin to WP ALS-PD or displaying many of the motor-system and behavioral changes of WP ALS-PD. It may be due to the presence of physiological levels of bicarbonate or of various toxic cofactors: bio-organic such as cycasin or inorganic such as pollutant metals e.g. aluminum or manganese, together with the lack of protective factors (e.g. calcium and magnesium deficiencies). Combined Al intoxication with Ca-Mg deficiencies is a reasonable model to investigate the pathogenesis of neurodegenerative diseases and eventually to screen their treatments. It may also be considered as a model of magnesium deficit, but it does not concern simple magnesium deficiency reversible with mere oral physiological magnesium supplementation. Magnesium deficiency cannot result in neurodegenerative disease. Combined Al intoxication with Ca-Mg deficiencies is not reversible through physiological oral magnesium supplementation. It therefore constitutes a type of experimental magnesium depletion model, instrumental in the investigation of the pathogenesis of magnesium depletion and in the screening of its still unknown possible treatments. (ABSTRACT TRUNCATED)
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PMID:Are age-related neurodegenerative diseases linked with various types of magnesium depletion? 951 30

Current epidemiological surveys in the Western Pacific (Guam, and Kii Peninsula and West New Guinea) have suggested that low calcium (Ca), magnesium (Mg) and high aluminum (Al) and manganese (Mn) in river, soil and drinking water may be implicated in the pathogenetic process of foci of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD). The condition of unbalanced minerals was experimentally mimicked in this study using rats. Male Wistar rats, weighing 200 g, were maintained for 60 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca diet plus high Al. Magnesium concentrations were determined in spinal cord and trabecular bone using inductively coupled plasma emission spectrometry (ICP). In the experimental group maintained on a low Ca, high Al diet, magnesium concentration of the spinal cord was lower than the group fed a standard diet. Also, magnesium concentration of lumbar vertebra showed lower values in the experimental group fed a low Ca, high Al diet than did those on a standard diet or low Ca diet without supplemental aluminum. Our data indicate that low Ca, high Al diet influences Mg concentration in bone and central nervous system (CNS) tissues and that a low Ca, high Al diet diminishes Mg in bone and CNS tissues, thereby inducing loss of calcification in bone and degeneration of CNS tissue due to alteration of the normal biological effects of Mg.
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PMID:Aluminum decreases the magnesium concentration of spinal cord and trabecular bone in rats fed a low calcium, high aluminum diet. 960 Jun 75

For a long time, aluminium has been considered as an indifferent element from a toxicological point of view. In recent years, it became clear that aluminium is a potential toxic agent in humans and has been implicated in the pathogenesis of several clinical disorders, such as dementia, respiratory tract disorders and allergic reactions. Chronic exposure to aluminium fumes, inhalation of aluminium and aluminium-oxide powder increase the risk to develop serious central nervous system pathology, in particular Alzheimer's disease and amyotrophic lateral sclerosis (ALS). In the present study, 3 experimental and 1 control group of rats were used to study the effects of aluminium on the central nervous system. Aluminium was injected intracisternally as a single dose (50 micrograms for group I, 100 micrograms for group II and 300 micrograms for group III) to the experimental groups (n = 5 in each group). The same dose was given at 3 months after the first injection to all groups. The control group (n = 5) was intracisternally given a physiological salt solution. Electromyography (EMG) was applied to the rats of the experimental groups. Rats were decapitated at 3 months after the second injections. Spinal cord samples from lumbar and cervical regions were removed and histological examination was performed. Light microscopical investigations revealed severe degeneration in motor neurons of the rats treated with 300 micrograms. Neurofibrillary tangle formation, chromatolysis and abnormal localization of the nuclei were found in swollen perikarya. Extreme loss of motor neurons with "ghost cell" appearance was found in that group. Sections of spinal cords of rats treated with lower doses of aluminium showed a moderate degree of motor neuron damage. EMGs of rats treated with the high dose of aluminium revealed severe acute denervation whereas treatment with lower doses resulted in moderate denervation. We conclude that aluminium may cause severe motor neuron damage in rat spinal cord resembling ALS.
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PMID:Motor neuron degeneration due to aluminium deposition in the spinal cord: a light microscopical study. 1033 62

The monthly intracisternal inoculation of aluminum chloride (AlCl3) to young adult New Zealand white rabbits induces motor neuron degeneration marked by intraneuronal neurofilamentous aggregates similar to that observed in amyotrophic lateral sclerosis (ALS). However, in contrast to ALS, this process occurs in the experimental paradigm in the absence of a glial response. In addition, whereas ALS is a fatal disorder, the cessation of aluminum exposure leads to both clinical and neuropathological recovery. Because microglia can influence neuronal regeneration, we have examined the effect of both acute and chronic aluminum exposure on microglial activation in vivo. We have studied microglial morphology in young adult New Zealand white rabbits receiving either single (1000 microg) or repeated sublethal (100 microg monthly) intracisternal inoculums of AlCl3. In addition, rabbits receiving 1000 microg AlCl3 inoculums were studied following an unilateral sciatic axotomy 48 h prior to the AlCl3 exposure. Our studies demonstrate that microglial activation in vivo is inhibited by AlCl3 exposure, and that a correlation exists between the extent of microglia suppression and the potential for recovery. This suggests that microglial activation is an important determinant of neuronal injury.
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PMID:A morphological analysis of the motor neuron degeneration and microglial reaction in acute and chronic in vivo aluminum chloride neurotoxicity. 1069 47

Epidemiological surveys in the foci of ALS of the Kii Peninsula of Japan started in the early 1960s. Continuous surveys conducted for decades revealed that there have been two foci in the Kii Peninsula: one in Kozagawa in the southern part, and the other in Hobara in the south-east. Clinically, ALS patients of the Kii foci occasionally showed parkinsonian features or dementia that have not been reported in the sporadic form of ALS. Neuropathologically, numerous NFT that are identical to those of Alzheimer's disease were observed in the cerebral cortex and in the brainstem nuclei. To elucidate the etiopathogenesis of this unique form of ALS, an analysis was conducted of the environment in the focus areas and of the specimens from the patients with ALS. It was hypothesized that the long exposure of these environments to low calcium and magnesium, and an excess of aluminum and manganese in the drinking water and the soil, might lead to the deposition of some trace elements in the CNS, eventually causing neuronal degeneration and death.
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PMID:Kii ALS dementia. 1139 74

This is a review of the literature on the effect of aluminum (Al) and its compounds on the nervous system. The role of aluminum in etiology of some degenerative diseases of the nervous system, e.g. Alzheimer disease, amyotrophic lateral sclerosis or dementia, is presented. The special attention was turned to the effects of aluminum on the nervous system functions in persons occupationally exposed to metal-containing dusts and fumes, manifested mostly by neurobehavioral disorders and changes in the brain bioelectric functions and less frequently pronounced by clinical neurological symptoms.
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PMID:[Nervous system disorders induced by occupational exposure to aluminium compounds: a literature review]. 1192 79

We analyzed the association between the environmental exposure to trace elements and the risk of sporadic amyotrophic lateral sclerosis (ALS) in a population-based case-control study in the Emilia-Romagna region in northern Italy. We evaluated exposure to selected trace elements by measuring toenail concentrations of the same by means of inductively coupled plasma optical spectrometry and instrumental neutron activation analysis. The final number enrolled in the study was 22 patients and 40 controls. Disease progression, assessed through a clinical score, was generally unassociated with toenail trace element levels, with the exception of an inverse relation with zinc and selenium content and a direct correlation with copper concentration. In logistic regression analysis, we found no evidence of an association between ALS risk and toenail content of cadmium, lead, copper, zinc, manganese, selenium, chromium, cobalt, iron, and aluminum. This investigation does not suggest a major role in sporadic ALS etiology of environmental exposure to these trace elements, though results for zinc, selenium, and copper should be evaluated with caution due to the potential limitations of toenails as biomarkers of chronic exposure in patients.
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PMID:Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: a population-based case-control study. 1212 44


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