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)

Antibodies to Ca channels in ALS patients IgG can be demonstrated to enhance Ca current and cause cell injury and death in a motoneuron cell line in vitro. To determine whether these antibodies can alter neuronal calcium homeostasis in vivo IgG fractions from six ALS patients were injected intraperitoneally into mice, and neurons assayed by ultrastructural techniques for calcium content. After 24 h, all six ALS IgG by (40 mg/animal) increased vesicle number in spinal motoneuron axon terminals, and in boutons synapsing on spinal motoneurons. Using the oxalate-pyroantimonate technique for calcium precipitation, these antibodies produced dose-dependent calcium increases either in axon terminal synaptic vesicles and mitochondria, or in rough endoplasmic reticulum, mitochondria, and Golgi complex of spinal motoneuron and frontal cortex pyramidal cells. ALS IgG was itself internalized and also induced neurofilament H phosphorylation. The observed changes in ultrastructure and calcium compartmentation were restricted to motoneurons; normal and disease control IgG, which did not possess antibodies enhancing calcium entry, did not exert similar effects. These data demonstrate that ALS IgG containing Ca-channel antibodies can alter calcium homeostasis of motoneurons in vivo.
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PMID:Antibodies to calcium channels from ALS patients passively transferred to mice selectively increase intracellular calcium and induce ultrastructural changes in motoneurons. 757 Mar 50

Numerous studies of amyotrophic lateral sclerosis have suggested that increased intracellular calcium is a common denominator in motoneuron injury. In experimental models, IgG from patients with amyotrophic lateral sclerosis enhanced calcium entry and induced apoptotic cell death in vitro as well as increased intracellular calcium and induced ultrastructural alterations of the motor nerve terminals in mice in vivo. To determine whether similar increases in intracellular calcium and altered morphology are present in motor nerve terminals of amyotrophic lateral sclerosis patients in vivo, muscle biopsy specimens from 7 patients with amyotrophic lateral sclerosis, 10 nondenervating disease control subjects, and 5 patients with denervating neuropathies were analyzed with ultrastructural techniques, employing oxalate-pyroantimonate fixation to preserve in situ calcium distribution. Motor nerve terminals from amyotrophic lateral sclerosis specimens contained significantly increased calcium, increased mitochondrial volume, and increased numbers of synaptic vesicles compared to any of the disease control groups, without exhibiting excess Schwann envelopment specific to denervating terminals. These results parallel the effect of amyotrophic lateral sclerosis IgG passively transferred to mice, and provide the first demonstration that neuronal calcium is, in fact, increased in amyotrophic lateral sclerosis in vivo.
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PMID:Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis. 896 52

4-Hydroxynonenal (4-HNE), a major lipid peroxidation product, induces oxidative stress, acts as an autonomous effector of cell death in motor neuron hybrid cell cultures, and is elevated in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). Elevation of the total intracellular calcium has also been demonstrated in motor axon terminals of ALS patients as well as in spinal motor neurons of animal models of familial and sporadic ALS. Since the association of intracellular calcium and oxidative stress has been suggested in ALS, the in vivo effect of intrathecally administered 4-HNE on the motor neuronal calcium level was examined in the spinal cord of rats. After 12 days of treatment, total intracellular calcium was assayed by electron microscopic histochemistry using the oxalate-pyroantimonate method. Morphology of spinal motor neurons was characterized by light and electron microscopy. In rats, 4-HNE treatment induced a mild impairment of gait, elevation of 4-HNE in the CSF, loss of spinal motor neurons, and reduction of total calcium in the surviving, structurally intact motor neurons. 4-HNE could only cause a lesion if glutathione synthesis was concomitantly inhibited in the animals. The results suggest that upstream components of the oxidative injury in relation to lipid peroxidation are necessary to compromise the glutathione system in ALS, allowing an increase of 4-HNE in the CSF, which further aggravates the primary oxidative lesion. The reduced intracellular calcium in the surviving motor neurons with no morphological features of degeneration may reflect an impaired ionic homeostasis, which may indicate a residual damage of an incomplete degenerative process.
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PMID:Sublethal dose of 4-hydroxynonenal reduces intracellular calcium in surviving motor neurons in vivo. 1593 71