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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We discuss the evidence, based on the analysis of transgenic mice overexpressing the human neurofilament (NF) heavy gene, that abnormal NF accumulations can provoke neurodegeneration of motor neurons. Transgenic mice overexpressing by two-fold the normal levels of human NF-H proteins develop a progressive motor neuron disease with several pathologic features reminiscent of those found in amyotrophic lateral sclerosis (ALS). A plausible mechanism for the selective motor neuron degeneration is that exceeding levels of NF-H cross-linkages impede transport of newly synthesized NF structures. The abnormal NF accumulations in perikarya and proximal axons is accompanied by a disruption in axonal transport of not only NF proteins but also of other components required for maintenance of axons. The relevance of the NF-H transgenics as a model of ALS is discussed in light of our current knowledge of motor neuron disease.
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PMID:Mice overexpressing the human neurofilament heavy gene as a model of ALS. 756 55

For nearly 70 years apoptosis has been known to be a form of cell death distinct from necrosis as well as an important regressive event during the normal development of the nervous system. For example, in the chick, mouse, rat and human approximately 50% of postmitotic neurons die naturally during embryonic or fetal development. It is generally accepted that neurons die during this period by apoptosis. After the period of naturally occurring cell death, the surviving neurons may undergo degeneration and death due to injury or disease later either during development or in adulthood. Recently, apoptosis has been suggested to be involved in the abnormal neuronal death that occurs following axonal injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's. Although little is known about the etiology of these diseases, progress is steadily being made toward understanding their underlying mechanisms. For diseases of spinal motoneurons, during the past two years gene mutations have been identified in patients with familial amyotrophic lateral sclerosis or spinal muscular atrophy. Furthermore, a number of in vitro, in vivo, and mutant animal models have been developed in order to study the factors which control motoneuron survival and/or death. Here, we review the morphological differences between necrotic and apoptotic cell death and some of the methods used to differentiate the two pathways. We also discuss motoneuron cell death during development, following injury and in disease, and its prevention by different agents, including neurotrophic factors.
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PMID:Apoptosis in the nervous system: morphological features, methods, pathology, and prevention. 757 66

In this paper, the autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. His clinical symptoms were slowly progressive spasticity, pseudobulbar palsy and character change. He died of sepsis 32 months after protracting the disease. The autopsy revealed severe atrophy of the frontal and temporal lobes. The histological findings were severe neuronal loss with gliosis in the precentral gyrus and left temporal lobe tip, loss of Betz cell, prominent demyelination throughout of the corticospinal tract, axonal swelling in the cerebral peduncule, severe degeneration of the amygdala, mild degeneration of the Ammon horn, normal substantia nigra, a few neuronal cells with central chromatolysis in the facial nerve nucleus and very mild neuronal cell loss in the spinal anterior horn. The anterior horn cell only occasionally demonstrated Bunina body by H & E and cystatin-C stainings, as well as, skein-like inclusion by ubiquitin staining. Thus, this is a case of uncommon amyotrophic lateral sclerosis (ALS) dominantly affecting the upper motor neuron including the motor cortex and temporal limbic system. In analysis of nine cases of putative primary lateral sclerosis in the literature, six cases showed loss of Betz cell in the precentral gyrus, and four cases very mild involvement of the lower motor neuron such as central chromatolysis and eosinophilic inclusion body. Degeneration of the limbic system was observed in two cases. We indicated a possible subgroup with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease dominantly affecting the upper motor neuron.
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PMID:[An autopsied case of dominantly affecting upper motor neuron with atrophy of the frontal and temporal lobes--with special reference to primary lateral sclerosis]. 761 64

This study presents evidence for retrograde axonal transport of exogenous albumin and transferrin in adult brainstem motor neurons, whereas plasma proteins are not transported in neonatal motor neurons. The plasma protein uptake in motor neurons was dose-dependent, suggesting a nonspecific (fluid-phase) uptake mechanism. Further evidence for nonspecific uptake of exogenous transferrin in the motor neuron was found in the presence of transferrin receptor only on the soma and not on the axon terminal. The immunoreaction product of the exogenous plasma proteins was localized as perinuclear granules in association with the lysosomal system, as verified by staining for the lysosomal marker cathepsin D and by ultrastructural examinations. The results suggest that albumin and transferrin derived from hepatic synthesis gain access to motor neurons nonspecifically by retrograde axonal transport, whereas transferrin derived from intracerebral synthesis specifically gains access to motor neurons due to receptor-mediated uptake at the soma of the neuron. The lack of plasma proteins in developing motor neurons suggests that retrograde axonal transport of plasma proteins has no significance for developing axons. Plasma proteins have a potential for transporting toxic metals to motor neurons. Intraneuronal uptake of aluminum-transferrin either by nonspecific uptake in axon terminals or by receptor-mediated uptake at the soma may have a role in the pathogenesis of the motor neuron disease amyotrophic lateral sclerosis.
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PMID:Age-dependent uptake and retrograde axonal transport of exogenous albumin and transferrin in rat motor neurons. 774 35

The presence of large neurofilamentous accumulations in the perikaryon and proximal axon of motor neurons in amyotrophic lateral sclerosis (ALS) suggests that the expression of this abundant cytoskeletal protein may be altered. We performed quantitative in situ hybridization for the low molecular weight neurofilament subunit (NF-L) messenger RNA in six cases of sporadic ALS and six controls. We found a 41% decrease (p < 0.02) in the NF-L mRNA levels in anterior horn cells in ALS, with a 60% decrease (p < or = 0.01) in alpha motor neurons. This alteration may represent a non-specific response to axonal or neuronal injury or, alternatively, reflect the regenerative activity of residual normal motor neurons. NF-L mRNA levels were consistently low (in the third and fourth quartiles) in spheroid-bearing motor neurons, indicating that the neurofilamentous accumulations observed in ALS are not likely the result of overexpression of the NF-L gene. Total neuronal polyadenylated mRNA levels were also 50% lower (p = 0.02) in anterior horn cells and 48% lower (p < or = 0.05) in alpha motor neurons in ALS, possibly reflecting a decrease in selected mRNA species in diseased motor neurons.
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PMID:Neurofilament light and polyadenylated mRNA levels are decreased in amyotrophic lateral sclerosis motor neurons. 790 36

Expression of chromogranin A in various neurological diseases was examined immunohistochemically using purified anti-human chromogranin A antiserum. The antibody stained dystrophic neurites in senile plaques in Alzheimer disease brain, Pick bodies and ballooned neurons in Pick's disease brain, some Lewy bodies in the substantia nigra of Parkinson's disease, and axonal swellings in various neurological conditions including Parkinson's disease, striatonigral degeneration, Shy-Drager syndrome, amyotrophic lateral sclerosis and cerebral infarction. The present study shows that expression of chromogranin A is not an exclusive feature of Alzheimer disease or Pick's disease, and indicates that it could be a useful marker for various neurological diseases.
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PMID:Expression of chromogranin A in lesions in the central nervous system from patients with neurological diseases. 804 89

Alz-50 is a monoclonal antibody that recognizes normal tau proteins as well as phosphorylated tau proteins that are associated with paired helical filaments in Alzheimer's disease. To establish an accurate baseline for future pathological studies, we examined the distribution of Alz-50 immunoreactivity in normal human brain from infancy to senescence. We found extensive staining patterns of somata and axonal profiles in the striatum, amygdala, hypothalamus, brainstem and spinal cord in all normals at all ages. Similar normal staining patterns were seen in the brains of patients who had suffered trauma, tumors, cerebral infarcts, grade 1 periventricular hemorrhages, and in those who had suffered from amyotrophic lateral sclerosis, Parkinson's disease, multi-systems atrophy and Shy-Drager syndrome. An absence of cell body staining and only minimal axonal staining was noted in the same brains with immunocytochemistry using PHF-1, a monoclonal antibody generated against paired helical filament proteins from Alzheimer brains. The characteristic staining pattern of Alz-50 in normal brains is substantially more extensive than has previously been recognized. This pattern, which presumably describes a specific class of tau proteins, must be distinguished from the pathological staining observed in neurodegenerative diseases.
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PMID:The distribution of Alz-50 immunoreactivity in the normal human brain. 823 10

Neuromuscular diseases occur in as many as 50% of patients infected with human immunodeficiency virus type 1 (HIV-1). All forms of neuromuscular disease have been reported, including axonal neuropathy, demyelinating neuropathy, mononeuropathy multiplex, polyradiculitis, ALS-like syndromes, disorders of neuromuscular transmission, myopathy, and toxic neuropathies due to medication side effects. Neuromuscular disease is often the presenting manifestation of HIV-1 infection. Infection with cytomegalovirus (CMV) is associated with different types of neuropathy including mononeuritis multiplex and polyradiculopathy. There is effective treatment for many of the associated disorders including chronic inflammatory demyelinating neuropathy, CMV-mediated neuropathies, and myopathy. Treatment of CMV-mediated mononeuropathy multiplex may be life saving. The different neuromuscular syndromes associated with different stages of HIV-1 infection may be due, in part, to different levels of immunocompetence.
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PMID:AAEM minimonograph #41: neuromuscular diseases associated with HIV-1 infection. 826 98

Contrary to the recently reemphasized notion that the primary neuron involved in amyotrophic lateral sclerosis (ALS) is the cortical (upper) motor neuron (UMN), we believe that the lower motor neuron (LMN) is primarily involved by the retrograde transport of pathogens from neuromuscular junctions, and the disease process spreads monosynaptically to the UMN. Pathologically and epidemiologically, the LMN hypothesis is more logical than the UMN in light of the recent understanding of neuroaxonal transport systems, particularly in regard to anterograde cytoskeleton transport and the kinetics of the force promoting slow axonal transport. By correlating the early pathologic findings, i.e., the swelling of the initial axons and formation of intracytoplasmic inclusions in the LMN, ALS may be regarded as a disease of axonal transport, especially its slow component (SCa). Therapeutic intervention to facilitate SCa should be attempted in ALS.
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PMID:Amyotrophic lateral sclerosis: lower motor neuron disease spreading to upper motor neurons. 833 39

Motorneurons which are primarily affected in ALS cannot be sampled during life. Morphological, biochemical, ultrastructural and molecular investigations can be only performed on post-mortem material. No animal model reproduce adequately ALS. All these features and the low ALS incidence and the absence of definite clusters stress the need for brain banking in Europe. We present the protocol which is followed in our centers. The clinical information is supplied by neurologists in order to provide clinical data necessary for an accurate interpretation of pathological features. Initial symptomathology, duration and type of ALS, cause of death and a simple disability scale shortly before death are included. CNS relevant samples stained with H-E, luxol fast blue, the Marchi impregnation technique and immunostained with ubiquitin, are used for diagnosis. Samples for Golgi impregnation and immunohistochemistry are also obtained and the remaining tissue is frozen. Classical criteria for pathological diagnosis include: neurogenic changes in muscles, loss of motorneurons and degeneration of corticospinal tracts. We propose new diagnostic criteria based only on CNS examination. Muscle tissue is not always available and other classical criteria could be absent in rapid evolution or early death cases. Our criteria includes: a) Major criteria: loss or degeneration (chromatolysis, basophilia or neuronophagia) of motorneurons in brainstem and/or spinal cord, degeneration of corticospinal tracts. b) Minor criteria: axonal spheroids, Bunina bodies, ubiquitin-immunoreactives bodies. Criteria necessary for the pathological diagnosis are discussed and the need to quantify neuronal loss in relation to age-matched controls is stressed.
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PMID:Amyotrophic lateral sclerosis brain banking: a proposal to standardize protocols and neuropathological diagnostic criteria. 836 Jun 61


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