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)

The distribution of intra-axonal corpora amylacea (IACA) in the CNS was studied in 2 cases of ALS, a hepatic encephalopathy and a Shy-Drager syndrome. A total of 149 IACAs were found. IACAs were observed far most frequently in the gracile nuclei, followed by the anterior horns of the spinal cord and in descending order; lateral geniculate bodies, reticular formation, sensory and motor nuclei in the brain stem, cerebellum and cerebral cortex. The basal ganglia, including the thalamus, contained only a few. IACA were not observed in the pyramidal tracts or in the spinal roots. About 3% of the IACA were sectioned longitudinally, together with the original small nerve fibres and abrupt enlargement of the axons due to the deposits was well demonstrated.
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PMID:Intra-axonal corpora amylacea in the CNS. 19 38

Hereditary canine spinal muscular atrophy is a newly recognized motor neuron disease occurring in Brittany Spaniels. The clinical manifestations, pattern of inheritance, electrodiagnostic findings, and muscle biopsies have features in common with human spinal muscular atrophy. Neuropathological examination discloses some loss of motor neurons in the spinal cord and brainstem. Many of the surviving motor neurons have neurofibrillary swellings in proximal axons, an abnormality similar to that which occurs early in the course of human amyotrophic lateral sclerosis. These axonal swellings are filled with maloriented skeins of neurofilaments. Since the proteins comprising neurofilaments are carried by slow axonal transport, their accumulation within axons suggest that the swellings may result from impaired slow transport, a hypothesis that can be tested in affected Brittany Spaniels. Hereditary canine spinal muscular atrophy is a new genetic, clinical, and pathological entity, and, at present, it appears to be the best currently available animal model of motor neuron disease.
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PMID:Hereditary canine spinal muscular atrophy. 43 62

The binding of lead to serum proteins was studied in vitro in ALS-patients and controls. Serum was incubated with 210Pb, the proteins were separated by isoelectric focusing and the radioactivity in the different protein fractions was determined by liquid scintillation counting. The activity was concentrated in the orosomucoid (acid alpha1-glycoprotein) fraction both in ALS-patients and controls under the present experimental conditions and the capacity of this protein to bind lead was demonstrated in a control experiment. The findings are discussed in relation to our earlier observations on increased concentrations of lead in cerebrospinal fluid and plasma in ALS-patients and the hypothetical role of the retrograde axonal transport in motoneurons in the pathogenesis of ALS. The present observations do not lend support to the idea that the increased plasma concentrations of lead in the disease would be related to qualitative differences in serum protein binding.
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PMID:Serum protein binding of lead in vitro in amyotrophic lateral sclerosis patients and controls. 69 Jun 66

We report here our studies on IgM reactivity towards peripheral nervous system gangliosides, in motor-neuron diseases (MND) without IgM gammopathies, and in peripheral neuropathies with IgM gammopathies. We showed by enzyme linked immunosorbent assay technique, that anti-GM1 IgM antibodies were often present at a low level in normal controls in contrast to anti-GD1b antibodies, which were never detected in control sera. We evidenced that several steps of the ELISA technique were critical such as the nonaddition of detergent in buffer solutions used for dilutions and for washing and the choice of the ELISA plates. We studied 50 cases of motor-neuron diseases, among which 40 typical cases of Amyotrophic Lateral Sclerosis, only a few had high anti-GM1 antibodies levels, which were always confirmed by immunodetection on thin-layer chromatography. These antibodies were generally directed against the oligosaccharide epitope present also in asialoGM1. No correlation has been as yet established in relation to the clinical state of the patients. In a few cases of polyneuropathies associated with IgM gammopathies, antiganglioside antibodies have been reported. We have found anti-GD1b antibodies to be present in a sensory-motor axonal neuropathy; axonal involvement was evidenced by electrophysiological study.
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PMID:Antiganglioside antibodies in motor-neuron diseases and peripheral neuropathies: study by ELISA technique and immunodetection on thin-layer chromatography. 133 72

Motoneurones are known to die (1) during embryonic development (naturally occurring cell death), (2) early in postnatal development after axonal injury, and (3) as a consequence of disease, such as spinal muscular atrophy or (in later life) amyotrophic lateral sclerosis. Naturally occurring motoneurone death has been extensively investigated, and interaction with the target muscle has emerged as an important factor for survival of embryonic motoneurones. Evidence that this target dependence of motoneurones continues postnatally is discussed in this review, as is the possible nature of the retrograde signal from the muscle. An explanation for the role of the muscle in motoneurone survival is also proposed, which may be applicable in situations where motoneurone death occurs postnatally. This proposal takes into account the changing functional demands imposed on motoneurones as a result of the gradual maturation of the CNS, and suggests that during development the muscle induces the motoneurones to become competent to carry out these requirements.
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PMID:Dependence of postnatal motoneurones on their targets: review and hypothesis. 137 20

beta,beta'-Iminodipropionitrile (IDPN) impairs axonal transport of neurofilaments; their accumulation leads to the formation of proximal swellings in motor axons. Similar proximal swellings are a feature of some cases of motor neuron disease such as amyotrophic lateral sclerosis (ALS). Motor units in IDPN-treated animals were assessed to determine their relative susceptibilities to impaired function and whether the functional changes resulting from proximal axonal swellings share certain electromyographic features with ALS. Intrinsic properties of medial gastrocnemius motoneurones (MN) and contractile responses of their motor units were examined during the evolution of proximal axonal swellings in cats administered IDPN (50 mg/kg once weekly) for 7, 14 or 35 days. While conduction velocities were significantly decreased in all motor unit types by 35 days, the conduction slowing was greater in fast fatigable (types FF and FI) motor units than in fatigue resistant (types FR and S) motor units. Normal correlations between axonal conduction velocity and MN input resistance (Rin) and the inverse relationship between Rin and rheobase were lost with progression of the neuropathy. Twitch and maximum tetanic tension developed by fast-fatigable motor units declined early in the neuropathy, whereas fatigue-resistant units did not show similar changes until later stages of the intoxication. In some motor units, irregular and abnormal tetanic tensions were elicited by repetitive MN discharge. At 14 and 35 days, a novel, intermediate motor unit response classified as slow and fatigable (SF) was observed. Conduction block, characterized by repetitive MN firing without a corresponding contractile response, was observed in some type FF and S units by 35 days. Morphometric analysis of muscle fiber types showed significant atrophy, particularly in the type I fibers at 14-35 days; the atrophy reversed following cessation of IDPN administration. The influence of proximal axonal swellings on motor unit function in IDPN neuropathy is discussed in terms of reported electrophysiological alterations in motoneurone disease.
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PMID:Motor unit function during evolution of proximal axonal swellings. 138 10

The distribution of mercury within the brainstem and spinal cord of mice was investigated with the autometallographic technique after intramuscular administration of a single dose of mercuric mercury (HgCl2). Deposits of mercury were localized to motor neurons of the spinal cord and to brainstem motor nuclei; i.e., neurons with their peripheral projections outside the blood-brain barrier. Unilateral ligation of the hypoglossal nerve prior to the injection of HgCl2 prevented the accumulation of mercury deposits in the ipsilateral hypoglossal nucleus. The selective accumulation of mercury in spinal and brainstem motoneurons is most probably due to a leakage of metal-protein complexes from capillaries in muscle into myoneural junctions, followed by uptake into nerve terminals and retrograde axonal transport. The possible link between this process and the development of motor neuron degeneration in ALS is discussed.
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PMID:Inorganic mercury is transported from muscular nerve terminals to spinal and brainstem motoneurons. 138 15

In amyotrophic lateral sclerosis (ALS), neuronal loss and axonal degeneration occur in motor neurons. Although there is limited axonal regeneration, surviving motor neurons send collateral sprouts to denervated muscle fibers. GAP-43, a protein enriched in growth cones and synaptic terminals, is thought to have a role in axonal elongation and synaptogenesis. GAP-43 messenger RNA (mRNA) expression was evaluated in ALS spinal cords using Northern blot analysis and in situ hybridization to assess whether surviving neurons can mount an appropriate response to injury. There was a two- to four-fold increase in GAP-43 mRNA in ALS that localized to the anterior horn cells. The increase in GAP-43 mRNA indicates that the mechanism which leads to degeneration in ALS does not compromise the neuron's capacity for vigorous expression of growth-associated proteins.
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PMID:GAP-43 gene expression is increased in anterior horn cells of amyotrophic lateral sclerosis. 138 17

We measured the diameter of the most distal portion of the axonal initial segment, the neuronal size of anterior horn cells, and the length of the axon hillock plus the initial segment (AH+IS) in the lumbar spinal cord in motor neuron disease. Three patients with amyotrophic lateral sclerosis (ALS) and one with lower motor neuron disease (LMND) were compared with 11 controls. Serial plastic sections stained with toluidine blue and electron micrographs were studied. A total of 214 axons directly emanating from the somata (n = 207) and the primary dendrites (n = 7) were observed in the patients. Approximately 19% of the proximal myelinated axons (24 axons out of 155 in ALS, and 17 axons out of 59 in LMND) were swollen at the first internode, and most of the swellings extended to the middle portion of the initial segment. Electron microscopy showed that the swellings of the proximal axons (the initial segment and the first internode) directly connected with their somata consisted mainly of accumulations of 10-nm neurofilaments. The average diameter of the most distal initial segment was markedly larger in ALS (n = 155) (P less than 0.0001) and LMND (n = 59) (P less than 0.0001) than in the controls (n = 258). Moreover, the average diameter of the most distal portion of even normal-appearing initial segments of the non-swollen axons was larger in ALS (n = 131) (P less than 0.0001) than in the controls. The perikarya and axon hillocks connected with the normal-appearing and swollen proximal axons and their dendrites almost always appeared normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increase in diameter of the axonal initial segment is an early change in amyotrophic lateral sclerosis. 150 50

The aim of this article is to emphasize the important role that copper plays in the function of nerve cells. We are reporting preliminary data which suggest that the swelling of axons which we produce in rats by iminodipropionitrile, IDPN, is due to its chelating action on copper, and how conversely supplementation with copper abolishes both symptoms and lesions. The copper values we obtained by atomic absorption spectrophotometry of the spinal cord and brain from the animals fully support this contention. In comparing these results with the diseases that are known to be due to copper deficiency, namely Menkes disease in man, swayback in lambs and several neurological mutant mice, we find not only similar axonal swellings, but also amelioration of symptoms and lesions by early administration of copper. Considering the main forms in which copper is present, we discuss the cuproproteins, i.e. ceruloplasmin and metallothionein, and their role in transport and delivery of copper to various organs. Further, the many cuproenzymes i.e. superoxide dismutase, tryptophan-2,3-dioxygenase, lysine oxidase, cytochrome oxidase, monoamine oxidases, tyrosinase, dopamine-beta-hydroxylase and d-amino levulinate dehydratase are noted for their roles in the nervous system. Finally, we suggest that neuronal copper deficiency should be more fully investigated as a possible etiological factor in the more common neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis, ALS.
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PMID:Deficiency of copper can cause neuronal degeneration. 161 61


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