Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyotrophic lateral sclerosis (ALS) usually presents as a sporadic disorder of motor neurons. However, familial forms of ALS have been described--autosomal dominant forms (ALS1, ALS3), clinically indistinguishable from the sporadic form, and autosomal recessive forms with early onset and slower progression of symptoms (ALS2). To localize the gene for one of the autosomal recessive forms of ALS, we applied linkage analysis to a large inbred family from Tunisia. A lod score maximum of Zmax = 8.2 at theta = 0.00 was obtained with marker D2S72 located on chromosome 2q33-q35. The fine mapping of this region suggested that the ALS2 locus lies in the 8 cM segment flanked by D2S155 and D2S115.
 ...
PMID:Linkage of recessive familial amyotrophic lateral sclerosis to chromosome 2q33-q35. 792 Jun 63

Additional genes in the growing ALS family of Candida albicans were isolated by PCR screening of a genomic fosmid library with primers designed from the consensus tandem-repeat sequence of ALS1. This procedure yielded fosmids encoding ALS2 and ALS4. ALS2 and ALS4 conformed to the three-domain structure of ALS genes, which consists of a central domain of tandemly repeated copies of a 108-bp motif, an upstream domain of highly conserved sequences, and a domain of divergent sequences 3' of the tandem repeats. Alignment of five predicted Als protein sequences indicated conservation of N- and C-terminal hydrophobic regions which have the hallmarks of secretory signal sequences and glycosylphosphatidylinositol addition sites, respectively. Heterologous expression of an N-terminal fragment of Als1p in Saccharomyces cerevisiae demonstrated function of the putative signal sequence with cleavage following Ala17. This signal sequence cleavage site was conserved in the four other Als proteins analyzed, suggesting identical processing of each protein. Primary-structure features of the five Als proteins suggested a cell-surface localization, which was confirmed by indirect immunofluorescence with an anti-Als antiserum. Staining was observed on mother yeasts and germ tubes, although the intensity of staining on the mother yeast decreased with elongation of the germ tube. Similar to other ALS genes, ALS2 and ALS4 were differentially regulated. ALS4 expression was correlated with the growth phase of the culture; ALS2 expression was not observed under many different in vitro growth conditions. The data presented here demonstrate that ALS genes encode cell-surface proteins and support the conclusion that the size and number of Als proteins on the C. albicans cell surface vary with strain and growth conditions.
 ...
PMID:Identification of Candida albicans ALS2 and ALS4 and localization of als proteins to the fungal cell surface. 976 64

The autosomal recessive form of juvenile amyotrophic lateral sclerosis (ALS2; RFALS Type 3) has previously been mapped to the 8-cM interval flanked by D2S115 and D2S155 on human chromosome 2q33-q34. We have established a yeast artificial chromosome (YAC) contig spanning an approximately 8-Mb region of the ALS2 candidate region and mapped 52 transcribed DNA sequences including 13 known genes and 39 expressed sequenced tags within this YAC contig. The establishment of a YAC contig and transcript map that spans the region containing the ALS2 mutation is an essential step in the identification of the ALS2 gene.
 ...
PMID:A yeast artificial chromosome-based physical map of the juvenile amyotrophic lateral sclerosis (ALS2) critical region on human chromosome 2q33-q34. 988 4

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular disease that shows familial, autosomal dominant inheritance in 10%-15% of cases. Previous genetic analysis of one large family linked a recessive form of familial ALS (FALS-AR type 3) to the chromosome 2q33-35 region. Using additional polymorphic markers, we have narrowed the size of the linked region to approximately 1.7 cM by linkage and haplotype analysis. We have also established a yeast artificial chromosome contig across the locus that covers an approximate physical distance of 3 million bases. Based on this contig, genes and expressed sequences that map near the 2q33 region have been examined to determine whether they are located within this ALS2 candidate locus. Five identified genes and 34 expressed sequence tags map within the region defined by crossover analysis and merit further consideration as candidate genes for this disease.
 ...
PMID:Refined mapping and characterization of the recessive familial amyotrophic lateral sclerosis locus (ALS2) on chromosome 2q33. 993 98

Autosomal recessive familial amyotrophic lateral sclerosis (RFALS) is a rare form of ALS that usually presents at an early age with slow progression of symptoms. RFALS is clinically and genetically heterogeneous and the locus of RFALS type 3 was mapped to 2q33 (ALS2) in a single family. We now report linkage of a more-common form of RFALS to chromosome 15q15-q22 markers (ALS5) and show further genetic locus heterogeneity in RFALS. ALS5 is the locus for most families with RFALS and appears to be present in both North African and European populations.
 ...
PMID:Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromosome 15q15-q22 markers. 993 1

Electrical and contractile properties of motor units (MU) were studied in the extensor carpi radialis muscles during voluntary contraction. The discharge of 234 single MUs was recorded in 11 patients with sporadic amyotrophic lateral sclerosis (ALS) and compared with that of the 260 MUs recorded in 12 healthy control subjects. Characteristics of the MU twitches and of the macro-potentials, the electromechanical coupling and the synchronization of the motor neurone discharges, were compared. In 5 patients (population ALS1), the twitch contraction force and macro-MUP area values were much larger than those of the controls. In the 6 other patients (population ALS2), the twitch force was considerably depressed, whereas the macro-MUP area was slightly, but significantly, increased. In ALS1, as well as in ALS2, the electromechanical coupling was much weaker than in the controls, and the fast-contracting MUs were more severely affected than the slowly contracting MUs. The motoneuronal synchronization was assessed by performing cross-correlation analysis on MUs discharges, and was used as an index to the strength of the common motoneuronal inputs. The rate of occurrence of synchronous firing was conspicuously lower in both populations of patients than in the control group. This might reflect the loss of corticospinal projections that occurs in ALS. The data are discussed in terms of the time course of motor neurone axonal sprouting, and in terms of the neuronal and muscular dysfunction possibly involved in ALS disease.
 ...
PMID:Electromechanical coupling and synchronous firing of single wrist extensor motor units in sporadic amyotrophic lateral sclerosis. 1040 Feb 12

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that manifests as selective upper and lower motor neuron degeneration. The autosomal recessive form of juvenile amyotrophic lateral sclerosis (ALS2) has previously been mapped to the 1.7-cM interval flanked by D2S116 and D2S2237 on human chromosome 2q33-q34. We identified three novel full-length transcripts encoded by three distinct genes (HGMW-approved symbols ALS2CR1, ALS2CR2, and ALS2CR3) within the ALS2 critical region. The intron-exon organizations of these genes as well as those of CFLAR, CASP10, and CASP8, which were previously mapped to this region, were defined. These genes were evaluated for mutations in ALS2 patients, and no disease-associated sequence alterations in either exons or intron-exon boundaries were observed. Sequence analysis of overlapping RT-PCR products covering the whole coding sequence for each transcript revealed no aberrant mRNA sequences. These data strongly indicate that ALS2CR1, ALS2CR2, ALS2CR3, CFLAR, CASP10, and CASP8 are not causative genes for ALS2.
 ...
PMID:Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2. 1116 14

Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease causing cell death of motor neurons and progressive muscle weakness. The disease is familial in ten percent of cases, of which one-fifth are due to mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Two papers in this issue of Nature Genetics describe homozygous mutations in a new gene on chromosome 2q33 in 4 families of Arabian origin with a rare form of juvenile onset ALS (ALS2). The predicted protein structure has domains homologous to GTPase regulatory proteins, and both the types of mutation and the pattern of inheritance suggest that motor neuron degeneration is the result of a loss of function. Further work will determine the relevance of this breakthrough to other, more common forms of ALS.
 ...
PMID:Genetic inroads in familial ALS. 1158 98

Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).
 ...
PMID:The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. 1158 85

The time constants and rheobase currents are properties of axonal membrane and their calculation may shed light on axonal properties when taken in conjunction with examinations of axonal excitability. Using double cable models of human myelinated motor and sensory axons and of their three simulated types amyotrophic lateral sclerosis (termed as ALS1, ALS2 and ALS3, respectively), the time constants and rheobase currents (nodal/internodal) are calculated in the case of action potential propagation and in the case of a uniformly polarized fibre. A polynomial function of degree 2 (parabola), which relates threshold charge to stimulus duration, provides an accurate fit for the axon data. The results are consistent with the interpretation that the considerably different nodal/internodal time constants and nodal/internodal rheobase currents depend not only on the cable properties of the axons, as well as on the nodes, but on the methods of stimulation.
 ...
PMID:Strength-duration properties of human myelinated motor and sensory axons in normal case and in amyotrophic lateral sclerosis. 1169 88


1 2 3 4 5 6 7 8 9 Next >>