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)

Reductions in glutamate and aspartate contents, together with increased contents of taurine, have been observed in the autopsied brains and spinal cords of patients who have died with amyotrophic lateral sclerosis (ALS). The wobbler mouse develops an inherited degeneration of motoneurons within the brainstem and spinal cord, and has been proposed as an animal model of ALS. In symptomatic wobbler mice we found brain contents of glutamate, aspartate, and taurine similar to those in unaffected littermates, while brain contents of glutamine were increased, and those of serine and alanine were decreased. Spinal cords of wobbler mice had slightly decreased contents of glutamate, aspartate and glycine compared to normal littermates. Abnormalities of amino acid contents in the nervous system of wobbler mice are dissimilar to those in ALS patients suggesting a different pathogenesis of motoneuron loss.
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PMID:The wobbler mouse: amino acid contents in brain and spinal cord. 191 46

We evaluated glutamine synthetase (GS) and alanine aminotransferase (GPT) activities in biopsied muscle from 40 cases of various neuromuscular diseases. GS and GPT catalyze the synthesis of glutamine and alanine, respectively, from amino acids derived in part from the breakdown of muscle proteins. The subjects were 7 cases of muscular dystrophy; 1 Duchenne type (DMD), 3 limb-girdle type, 2 facioscapulohumeral type (FSH), 1 Fukuyama type (FCMD); and 1 myotonic dystrophy (MyD); 5 mitochondrial myopathies; 11 inflammatory myopathies including 6 polymyositis and 3 myopathy associated with collagen disease; 5 endocrinological myopathies including 2 periodic paralysis; and, 11 cases of neurogenic amyotrophies [4 amyotrophic lateral sclerosis (ALS), 4 spinal progressive muscular atrophy (SPMA) and 3 other types]. Control subjects were 8 patients with thigh operations. Biopsied muscle was homogenized and assayed for GS activity by the method of Smith et al.; GPT was assayed by commercial kit. Protein was assayed by the method of Lowry et al. Enzyme activities between mean -2SD and mean +2SD of controls were considered to be the normal range. GS activity in control subjects was 28.22 +/- 7.13 (mean +/- SD) nmol glutamine formed/mg protein/hr. Fifteen of 40 cases showed increased enzyme activity, including DMD and FCMD, the acute phase of polymyositis, and periodic paralysis. GPT activity in controls was 16.56 +/- 4.05 IU/mg protein. Sixteen of 40 patients showed increased enzyme activity: FCMD, FSH, MyD, inflammatory and endocrinological myopathy, and ALS. On the other hand, mitochondrial myopathy showed significantly decreased activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies on enzyme activities relating to amino acid mobilization in biopsied muscles]. 198 Jun 44

Amino acid contents were measured in autopsied brains of eight patients with the sporadic form of amyotrophic lateral sclerosis (ALS) and in brains of control subjects dying without neurologic or psychiatric disease. Glutamic acid content was reduced in most brain regions and in the cervical cord in the ALS patients, while glutamine contents were normal. Taurine contents were increased, and gamma-aminobutyric acid contents were decreased in some brain regions in the ALS patients. The brain glutamate deficiency in ALS is unexplained, but insufficient production or release of this excitatory neurotransmitter might have important secondary effects on motor neurons.
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PMID:Brain glutamate deficiency in amyotrophic lateral sclerosis. 289 Oct 83

Because recent studies showed a systemic defect in glutamate metabolism in amyotrophic lateral sclerosis (ALS), we measured the levels of free amino acids in frontal and cerebellar cortex and two areas of spinal cord obtained at autopsy from 22 patients who died of this disease. Glutamate levels were significantly decreased (by 21 to 40% of control values) in all areas investigated; cervical and lumbar spinal cord showed the greatest change. Aspartate levels were also significantly reduced (by 32 to 35%) in the spinal cord only. A positive correlation was shown between the changes of glutamate and aspartate as well as a significant alteration in the glutamate to glutamine ratio in the spinal cord of patients with ALS. Although we cannot exclude the possibility that these abnormalities may partly result from neuronal cell loss, the data suggest the presence of a generalized defect that may affect the neurotransmitter and metabolic pool of glutamate. The defect may be expressed more severely in the spinal cord than in other central nervous system areas. These results, taken together with the previously shown systemic abnormality, raise the possibility that distribution of glutamate between the intracellular and extracellular pool may be altered in ALS and may mediate the neurodegeneration.
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PMID:The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis. 290 29

A high-performance liquid chromatography (HPLC) method is described for determining subpicomole concentrations of beta-N-methylamino-L-alanine (BMAA) in plant and animal tissue. BMAA and other amino acids were reacted with 9-fluorenylmethyl chloroformate (FMOC) for 10 min under alkaline conditions to form highly fluorescent and stable derivatives. All amino acids, including BMAA, eluted from the column within 22 min. BMAA (tr = 18.02 +/- 0.07 min) was detected in Cycas circinalis L. seed and in serum, cerebrospinal fluid and brain tissue from BMAA-treated monkeys and rats. The primary amino acids glutamine, glutamic acid, aspartic acid, alanine, glycine and gamma-aminobutyric acid (GABA) could also be detected since they were well resolved from BMAA. These amino acids and BMAA were linear over the concentration range of 0.15-7.5 microM with a relative standard deviation ranging from 2.1-6.7%. This method should prove useful in studies to determine the role of BMAA in the Western Pacific amyotrophic lateral sclerosis/Parkinsonism-dementia complex for which cycad seed is the principal etiological candidate.
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PMID:Determination of beta-N-methylamino-L-alanine (BMAA) in plant (Cycas circinalis L.) and animal tissue by precolumn derivatization with 9-fluorenylmethyl chloroformate (FMOC) and reversed-phase high-performance liquid chromatography. 319 47

The spinal muscular atrophies (SMAs) are defined as a group of inherited disorders sharing the common pathological feature of degeneration of the anterior horn cells of the spinal cord and, in some cases, additionally of the bulbar motor nuclei. They are classified according to clinical features, including severity and distribution of muscle weakness and on their modes of inheritance. The SMAs are not uncommon: SMA type I (severe, acute infantile SMA) alone has a gene frequency in the UK estimated at 0.006. Together they represent a significant source of morbidity and mortality. Over the past 3 years, two major advances have been made towards understanding the molecular basis of these clinically heterogeneous disorders. First, in 1990, it was reported that all three forms of childhood-onset proximal SMA were linked to probes mapping to the proximal long arm of chromosome 5. Significant progress has been made towards isolating the gene or genes responsible, and a protocol for prenatal disease prediction in families with a previously severely affected child has been established. Second, in 1991, the molecular defect in adult-onset X-linked spinal and bulbar muscular atrophy was defined as an expansion of a (CAG)n trinucleotide repeat which encodes a string of glutamine residues in the first exon of the androgen receptor. Little progress has been made in elucidating the molecular pathology of the other SMAs. None of them has been linked to chromosome 5q markers, or indeed to markers elsewhere; the conditions are rare and pedigrees generally small. When the gene (or genes) on proximal 5q underlying SMA types I, II and III is cloned, mutations in this can then be sought in the other SMAs. The product of the chromosome 5q gene presumably plays a crucial role in maintaining the integrity of motor neurones, so determination of its structure and function may well have consequences far beyond those pertaining to the inherited SMAs. The identification of pathogenic mutations in the SOD-1 gene in familial amyotrophic lateral sclerosis is of great interest, although it is not clear that similar mechanisms contribute to the more common sporadic form of the disease.
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PMID:Disorders of the motor neurone. 795 56

Data from the literature about plasma and CSF amino acid (AA) levels in amyotrophic lateral sclerosis (ALS) remain controversial. To refine such analyses we used HPLC, and report a study of plasma and CSF AA concentrations in patients with ALS, the type of the disease (spinal and bulbar onset) being precisely determined. In ALS, there is a decrease in the plasma levels of the large neutral amino acids (LNAA) alanine, isoleucine, leucine, methionine and tyrosine which was particularly striking in the bulbar type (p < 0.05). Plasma glutamate levels do not differ between ALS and controls, but are significantly increased in ALS with spinal onset and decreased in the bulbar type (p < 0.05 vs controls, p < 0.001 bulbar vs spinal). In CSF, the analysis of the whole ALS group shows no difference from controls. However, there is an increase of CSF serine, glutamine and alanine in ALS with spinal onset (p < 0.05). Our results do not support an abnormal profile of excitatory AA concentrations in ALS. The heterogeneous changes we observed, mainly concerning LNAAs, may be explained by a blood-CSF barrier disturbance in the disease. As AA levels clearly differ between ALS types, with low concentrations in bulbar ALS, this dual profile probably explains some of the discrepancies between previous studies.
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PMID:Fasting plasma and CSF amino acid levels in amyotrophic lateral sclerosis: a subtype analysis. 808 43

Since recent studies provided evidence for abnormal glutamate metabolism in amyotrophic lateral sclerosis, we measured amino acid levels in the fasting plasma of 52 ALS patients and an equal number of controls of a similar age. In addition, the content of amino acids, N-acetyl-aspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG) were measured in spinal cord and brain tissue obtained at autopsy from patients dying of ALS. Results showed significant elevations (by about 70%) in the plasma levels of glutamate in the ALS patients as compared to controls. In contrast, glutamate levels were significantly decreased in all CNS regions studied of ALS patients (by 21-40%), with the greatest changes occurring in the spinal cord. The ratio of glutamine to glutamate was altered significantly in the spinal cord ALS tissue. In addition, reductions in the levels of aspartate (by 32-35%), NAA, and NAAG (by 40-48%) were found in the spinal cord of ALS patients. These results are consistent with a generalized defect in the metabolism of neuroexcitotoxic amino acids. An altered distribution of these compounds may occur between their intracellular and extracellular pools with resultant abnormal potentiation of excitatory transmission mediated by glutamate receptors and selective degeneration of motor neurons.
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PMID:Altered metabolism of excitatory amino acids, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate in amyotrophic lateral sclerosis. 845 87

To reconcile the autoimmune and excitotoxic hypotheses regarding the etiology of amyotrophic lateral sclerosis (ALS), we injected rats intraperitoneally with ALS immunoglobulins and monitored CSF glutamate, aspartate, glutamine, and glutathione. CSF glutamate was significantly increased at 24 and 72 hours compared with both basal levels and disease control injected rats. CSF aspartate was increased at 72 hours. Glutamine and glutathione were unchanged. These data suggest that ALS immunoglobulins may enhance CSF glutamate and aspartate levels and contribute to motoneuron injury.
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PMID:Increased CSF glutamate following injection of ALS immunoglobulins. 915 55

Approximately 20% of cases of familial amyotrophic lateral sclerosis are caused by dominant mutations in the Cu,Zn superoxide dismutase. One such mutant, in which histidine #48 has been replaced by glutamine (H48Q), exhibits a novel activity. It can react sequentially with O2- and H2O2 to generate a potent oxidant at its active site, possibly Cu(II)-OH, which then can oxidize urate to the corresponding radical. This O2- -dependent peroxidase activity exerted on a substrate peculiar to motor neurons may be the toxic gain of function which leads to the deleterious consequences of this mutation. G93A, G93R, and E100G were also examined and found not to exert this O2- -dependent peroxidase activity.
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PMID:Superoxide-dependent peroxidase activity of H48Q: a superoxide dismutase variant associated with familial amyotrophic lateral sclerosis. 934 73


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