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)

We examined median somatosensory evoked potentials (SEPs) in 26 patients with sporadic motor neuron disease (MND). SEPs were recorded with multiple scalp derivations, using both the midfront and the earlobe as references for each subject. Central conduction time (CCT) was abnormal in three patients, but only when using the midfront reference. Moreover, an exclusive alteration of the early prerolandic potentials (absent or delayed P20 and/or P22) was noted using the earlobe reference in amyotrophic lateral sclerosis and in progressive bulbar palsy (54% and 50% of patients, respectively) but not in progressive muscular atrophy. These findings correlated with clinical evidence of upper motor neuron signs and with the severity of the disease. In agreement with recent views regarding the sources of the early anterior cortical responses, neuronal loss in the motor cortex may be considered as affecting the generator sites of these potentials.
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PMID:Far-field and cortical somatosensory evoked potentials in motor neuron disease. 232 1

The involvement of sensory pathways in patients suffering from amyotrophic lateral sclerosis (ALS) is well reported in histopathological studies. Several laboratories have also used evoked potentials to evidentiate subtle dysfunctions of sensory systems in such patients. However, conflicting results have been presented in studies using evoked potentials. In the present experiment we have evaluated multimodality evoked potentials in subjects with sure diagnosis of sporadic ALS, by means of the Bonferroni multiple comparisons procedure. Our principal findings are: a) no statistical difference between patients and controls in BAEP and VEP recordings; b) a reduction of N13 amplitude and a prolonged P22 latency in SEP recordings. Due to the sources of N13 and P22, these latter alterations, however, do not implicate the involvement of somatosensory pathway. In conclusion, the current investigation does not provide an electrophysiological support for the involvement of sensory systems in the sporadic ALS.
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PMID:Multimodality evoked potentials in sporadic amyotrophic lateral sclerosis: a statistical approach. 849 58

We have shown in a mouse model of motor neuron disease, the legs-at-odd-angles (Loa) mutant, and that mutations in the cytoplasmic dynein heavy chain gene (Dnchc1) cause motor neuron degeneration. Mice exhibiting the Loa phenotype suffer progressive loss of locomotor function and homozygous animals have neuronal inclusion bodies that are positive for SOD1, CDK5, neurofilament and ubiquitin proteins. As this phenotype models some aspects of human motor neuron degeneration disorders, we think there is a reasonable likelihood that dynein may be a causative gene or susceptibility factor in human motor neuron disease. Therefore we have screened exons of this gene in a set of human patients with familial forms of disparate motor neuron degeneration diseases, affecting both upper and lower motor neurons: amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and hereditary spastic paraplegia. As part of this study, we have determined that DNCHC1 is a large gene of 78 exons spanning 86 kb genomic length. We have focused on the exons known to be mutated in Loa, and in a very similar mouse mutation, cramping 1 (Cra1); both mutations result in loss of anterior horn cells. The exons studied are highly conserved in a wide range of eukaryotes. We screened our patient samples by sequencing and although we detect single nucleotide polymorphisms, our results show these occur at the same frequency in our patient group as in control samples of unaffected individuals. Therefore we do not find any association between familial motor neuron disease and the genotypes presented here in the exons screened.
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PMID:No association with common Caucasian genotypes in exons 8, 13 and 14 of the human cytoplasmic dynein heavy chain gene (DNCHC1) and familial motor neuron disorders. 1312 1

The authors report mutation screening of the p150 subunit of dynactin (DCTN1) and the cytoplasmic dynein heavy chain (DNCHC1) genes in 250 patients with ALS and 150 unrelated control subjects. Heterozygous missense mutations of the DCTN1 gene were detected in one apparently sporadic case of ALS (T1249I), one individual with familial ALS (M571T), two patients with familial ALS, and two unaffected relatives in the same kindred (R785W). The allelic variants of the DCTN1 gene may represent a previously unknown genomic risk factor for ALS.
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PMID:Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. 1532 53

RNA-binding proteins (RBPs) are involved in many aspects of mRNA metabolism such as splicing, nuclear export, translation, silencing, and decay. To cope with these tasks, these proteins use specialized domains such as the RNA recognition motif (RRM), the most abundant and widely spread RNA-binding domain. Although this domain was first described as a dedicated RNA-binding moiety, current evidence indicates these motifs can also engage in direct protein-protein interactions. Here, we discuss recent evidence describing the interaction between the RRM of the trypanosomatid RBP UBP1 and P22, the homolog of the human multifunctional protein P32/C1QBP. Human P32 was also identified while performing a similar interaction screening using both RRMs of TDP-43, an RBP involved in splicing regulation and Amyotrophic Lateral Sclerosis. Furthermore, we show that this interaction is mediated by RRM1. The relevance of this interaction is discussed in the context of recent TDP-43 interactomic approaches that identified P32, and the numerous evidences supporting interactions between P32 and RBPs. Finally, we discuss the vast universe of interactions involving P32, supporting its role as a molecular chaperone regulating the function of its ligands.
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PMID:Interactions between RNA-binding proteins and P32 homologues in trypanosomes and human cells. 2638 42

Amyotrophic lateral sclerosis (ALS) is a late-onset, neurodegenerative disease associated with the loss of motor neurons in the spinal cord, brain stem and primary motor cortex. Deficit in the motor function is one of the clinical features of this disease. However, the association between adverse morphological alterations in the spinal motor neurons and motor deficit in sporadic ALS (SALS) is still debated. The present study has sought to investigate the effects of serial intrathecal injections of ALS-CSF into rat pups, at post-natal (P) days 3, 9 and 14, on the motor neuronal (MN) morphology at the cervical and lumbar levels of the spinal cord at P16 and P22. The present study used Cresyl violet and Golgi-Cox staining methods to determine the progressive changes in the morphology of spinal MNs in both cervical and lumbar extensions. The study found a loss of motor neurons in the spinal cord (36% for P16 in cervical and 41.7% in P16 lumbar and 49.57% for P22 cervical and 44.63% for P22 lumbar) and reduced choline acetyl transferase (ChAT) expression after repeated infusion of ALS-CSF. Significant increase in the soma area was also found in ALS-CSF rats (around 21% in P22 cervical and 26.4% in P22 lumbar). Soma hypertrophy was associated with increased dendritic arborization of MNs at both cervical and lumbar levels of the spinal cord. The data also showed a direct correlation between ALS-CSF induced changes in the MN number in the spinal cord and motor behavioral deficits. The loss of MNs, reduced ChAT, changes in soma and dendritic morphology with declined rotarod performance, thus, confirming the pathological phenotypes as seen in ALS patients.
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PMID:ALS-CSF-induced structural changes in spinal motor neurons of rat pups cause deficits in motor behaviour. 3317 Mar 40