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)

Many studies have established the central involvement of the Golgi apparatus in the transport and processing of plasma membrane, lysosomal, and secreted proteins. The Golgi apparatus of neurons is also involved in the axoplasmic flow of fast-moving macromolecules and in the orthograde, retrograde, and transsynaptic transport of exogenous ligands. Markers of the Golgi apparatus, based on traditional methods of enzyme cytochemistry, are not applicable to human tissues obtained at autopsy. For that reason, the Golgi apparatus of brain cells has not been examined adequately in diseases of the human nervous system. Here we report that an antiserum raised against MG-160, a 160-kDa sialoglycoprotein of medial cisternae of the Golgi apparatus of several rat cells, is a specific and easily reproducible immunocytochemical marker of the Golgi apparatus of human neurons and other cells obtained at autopsy. Application of this probe in amyotrophic lateral sclerosis has shown a fragmentation of the Golgi apparatus in motor neurons similar to that induced by depolymerization of microtubules. We suggest that the fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis has functional implications because significant reductions of secretion of insulin and immunoglobulins have been observed in islet cells and plasma cells, respectively, treated with microtubule-disrupting agents.
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PMID:Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis revealed by organelle-specific antibodies. 234 44

Recent immunocytochemical and morphometric studies with an organelle-specific antiserum against MG-160, an intrinsic membrane sialoglycoprotein of the Golgi apparatus, have shown in several patients with sporadic amyotrophic lateral sclerosis (ALS), and in a few patients with related conditions, a fragmentation of the Golgi apparatus of spinal cord motor neurons which resembles the dispersion of the organelle observed in cells treated with microtubule depolymerizing agents. In the present study we examined by morphometry the effect of tissue fixation and processing on the immunocytochemical morphology of the Golgi apparatus of motor neurons from spinal cords of five controls and in one patient with leptomeningeal lymphoma. Qualitative studies of the Golgi apparatus of spinal cord motor neurons were also carried out in two more individuals with lymphoma or leukemia with leptomeningeal involvement and in one patient with multiple myeloma associated with a chronic inflammatory demyelinating polyneuropathy. The results of this study show that it is possible to obtain optimal immunocytochemical preparations of the Golgi apparatus of spinal cord motor neurons in routinely fixed and processed tissues obtained at autopsy. This study also provides baseline values of the Golgi apparatus in normal individuals which may be useful in future studies of the organelle in human neuropathologic conditions affecting the lower motor neuron unit. Lastly, this study shows that the fragmentation of the neuronal Golgi apparatus is not limited to ALS and related disorders.
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PMID:On the significance and reproducibility of the fragmentation of the Golgi apparatus of motor neurons in human spinal cords. 774 32

The importance of the Golgi apparatus in the transport, processing, and targeting of proteins destined for secretion, plasma membranes, and lysosomes has emerged from numerous studies. In this paper we review studies from our laboratory dealing with 1) the Golgi apparatus during mitosis and the role of microtubules in maintaining the structure of the organelle, 2) the endocytosis of antibodies, exogenous lectins, and toxins into the Golgi apparatus of several cells including neurons in vivo and in vitro, 3) the traffic of MG-160, a membrane sialoglycoprotein of the medial cisternae of the Golgi apparatus, from the trans-Golgi network to the Golgi cisternae, and 4) the involvement of the Golgi apparatus of motor neurons in the pathogenesis of amyotrophic lateral sclerosis. We conclude with a summary of ongoing work on the primary structure of MG-160 and introduce evidence suggesting that this intrinsic membrane protein of the Golgi apparatus may be involved in the regulation of endogenous, autocrine, basic fibroblast growth factor. We hope that this review will stimulate studies on the Golgi apparatus of neurons, which may lead to the discovery of neuron-specific properties of this important organelle and its involvement in the pathogenesis of neurodegenerative disorders.
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PMID:Rous-Whipple Award Lecture. Contributions to the physiology and pathology of the Golgi apparatus. 794 66

Recent immunocytochemical and morphometric studies in amyotrophic lateral sclerosis, Alzheimer's disease (AD), and aging indicate that the neuronal Golgi apparatus is a reliable index of activity or degeneration. To further evaluate a possible role of the Golgi apparatus in the pathogenesis of AD, we examined by double labeling the neuronal Golgi apparatus, neurofibrillary tangles (NFTs), and senile plaques (SPs) in the hippocampus of six cases of AD, and in 13 controls including three cases of a rare form of dementia lacking distinctive histopathological features. The Golgi apparatus was visualized with a polyclonal antiserum against MG-160, a membrane sialoglycoprotein of the organelle, and NFTs and SPs were visualized with biotinylated basic fibroblast growth factor (bFGF). Only a rare SP contained a few small immunostained elements of the Golgi apparatus. Neurons with intracellular NFTs, labeled with biotinylated bFGF, contained intensely labeled but deformed Golgi apparatus, which was displaced by the NFTs and coalesced into larger irregular granules. In contrast, a population of neurons without NFTs displayed fragmentation of the Golgi apparatus, ie, the organelle appeared in the form of small round, disconnected, and dispersed elements instead of the normal perinuclear network of irregular or linear profiles which often extended into the proximal segments of dendrites. In addition, the fragmented neuronal Golgi apparatus was atrophic as the percentage of the cell surface area occupied by the organelle was 4.4 +/- 0.6% SD, whereas in neurons with a normal Golgi apparatus the percentage of the cell surface area occupied by the organelle was 10.3 +/- 0.3% SD. The results of this study suggest that in AD the Golgi apparatus of a population of neurons without NFTs is involved in the pathogenesis of the disease. Considering the role of the Golgi apparatus in the processing of polypeptides destined for fast axoplasmic transports, the fragmentation of the organelle may be associated with functional and structural impairments of axons and presynaptic terminals.
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PMID:In Alzheimer's disease the Golgi apparatus of a population of neurons without neurofibrillary tangles is fragmented and atrophic. 857 97

The Golgi apparatus (GA) of spinal cord motor neurons is fragmented in sporadic amyotrophic lateral sclerosis (ALS), and in asymptomatic and symptomatic transgenic mice expressing the G93A mutation of the gene of the human Cu,Zn superoxide dismutase, found in certain cases of familial ALS (FALS) [Gonatas NK (1994) Am J Pathol 145:751-761; Mourelatos Z, et al. (1996) Proc Natl Acad Sci USA 93:5472-5477]. A similar fragmentation of the GA has been described in cells treated with microtubule-depolymerizing drugs, where the organelle is functional and contains both Golgi stacks and trans-Golgi network (TGN), the compartment of exit and targeting of proteins processed by the GA. To gain a better definition of the structure of the fragmented neuronal GA in ALS, four cases of sporadic ALS with numerous Bunina bodies in spinal cord motor neurons were stained with antibodies against human TGN and against the lumenal and cytoplasmic domains of MG160, a protein of the medial cisternae of the GA. The fragmented GA was stained with the three antibodies, indicating the presence of both Golgi stacks and TGN. Furthermore, the staining of the fragmented GA by the antiserum against the cytoplasmic domain of MG160 indicates that the fragmentation of the GA is not the result of a terminal and global cytoplasmic lytic event. The Bunina bodies were not stained by the anti-MG160 antibodies, suggesting that they are not derived from the GA. The perikarya of neurons with fragmented GA showed normal immunoreactivity with antibodies against the heavy neurofilament subunit and alpha-tubulin. However, because of the lack of appropriate antibodies the localization of proteins such as spectrin, ankyrin, centractin and others which link the microtubules with the GA were not done. The findings support the hypothesis that, in ALS, the fragmented neuronal GA is functional. Additional work with animal models of ALS may establish whether the fragmentation of the GA is a sign of early degeneration or a compensatory reaction of the injured motor neuron.
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PMID:The fragmented neuronal Golgi apparatus in amyotrophic lateral sclerosis includes the trans-Golgi-network: functional implications. 954 89

The Golgi apparatus (GA) of the large pyramidal motor neurons in the cerebral cortex (Betz cells), was examined in sixteen patients with sporadic amyotrophic lateral sclerosis (ALS), in one patient with familial ALS (FALS), and in ten non-ALS age matched controls including one patient with Huntington's disease and one patient with a brain infarct. The GA was immunostained with an antibody against the MG-160 protein, a conserved sialoglycoprotein of the medial cisternae of the organelle. In ALS, 13.2% of counted Betz cells had fragmented GA in contrast to 0.6% in the ten non-ALS controls. The fragmentation of the GA of Betz cells was identical to that previously reported in spinal cord motor neurons from patients with sporadic ALS and in transgenic mice expressing the G93A mutation of the gene encoding the Cu/Zn superoxide dismutase. The striking morphological similarity between the fragmentation of the GA observed in Betz cells and in spinal cord motor neurons suggests that a similar pathogenic mechanism is responsible for both, and that the fragmentation of the GA of the spinal cord motor neurons is not a consequence of deafferentation due to the degeneration of the Betz cells.
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PMID:Fragmentation of the Golgi apparatus of Betz cells in patients with amyotrophic lateral sclerosis. 1022 16

The Golgi apparatus (GA) of the anterior horn cells in the spinal cord was examined by immunohistological methods with an antibody against the MG-160 protein, a conserved intrinsic membrane sialoglycoprotein of the medial cisternae of the GA, in three patients with familial amyotrophic lateral sclerosis (FALS) with posterior column involvement. Large motor neurons in the anterior horns were markedly reduced in number and 10 of total 14 remaining large motor neurons showed fragmentation and a reduction in the number of the elements of the GA. The fragmentation of the GA was identical to that previously reported in motor neurons of the spinal cord and motor cortex from patients with sporadic ALS and in transgenic mice expressing the G93A mutation of the gene encoding the Cu/Zn superoxide dismutase months before the onset of paralysis. This is the first report of fragmented GA of the anterior horn cells in patients with FALS with posterior column involvement. The findings suggest that the GA is a common target in the neuronal degeneration in sporadic and FALS.
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PMID:Fragmentation of the Golgi apparatus of the anterior horn cells in patients with familial amyotrophic lateral sclerosis with SOD1 mutations and posterior column involvement. 1072 99

We examined the Golgi apparatus (GA) of motor neurons of patients with ALS and in mice models of ALS by immunohistological method using antiserum against MG160 and against components of the trans-Golgi network (TGN46). The GA of half of the remaining spinal cord motor neurons of patients with sporadic ALS showed fragmentation, where the GA were dispersed or fragmented into numerous small, isolated elements. The GA of Betz cells in sporadic ALS were fragmented similar to that of anterior horn cells, and the GA of spinal cord motor neurons of those with familial ALS and of those with ALS with basophilic inclusions were fragmented or diminished. The GA in the majority of the motor neurons contained Bunina bodies, basophilic inclusions and superoxide dismutase 1 (SOD1)-positive aggregates were fragmented. The motor neurons in transgenic mice expressing G93A mutation of the SOD1 gene showed the fragmentation of the GA months before the onset of paralysis. These findings suggest that the fragmentation of GA may be related to the neuronal degeneration in patients with ALS.
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PMID:Golgi apparatus of the motor neurons in patients with amyotrophic lateral sclerosis and in mice models of amyotrophic lateral sclerosis. 1638 90

We have previously shown in our laboratory that cerebrospinal fluid from ALS patients (ALS-CSF) contains putative toxic factor(s). In the present study we determined the effect of ALS-CSF on the integrity of the Golgi apparatus of spinal motor neurons in the neonatal rats. CSF was injected intrathecally into three-day-old rat pups and subsequently the ultrastructural changes in the motor neurons were studied after 48 h, 1, 2 and 3 weeks. We observed that ALS-CSF causes fragmentation of the Golgi apparatus in a considerable number of motor neurons in the spinal cord. This was further confirmed when motor neurons were stained with an antibody against a medial Golgi protein (MG160). Thus, we suggest that the putative toxin(s) present in ALS-CSF may cause impairment in the protein processing leading to motor neuron death.
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PMID:Cerebrospinal fluid from amyotrophic lateral sclerosis patients causes fragmentation of the Golgi apparatus in the neonatal rat spinal cord. 1745 33