Disease relevance of Amyotrophic Lateral Sclerosis

• We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons [1].
• Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and prion diseases are increasingly being realized to have common cellular and molecular mechanisms including protein aggregation and inclusion body formation [2].
• In this review, we discuss the current status of genetic epidemiology of the most common neurodegenerative diseases: Alzheimer disease, Parkinson disease, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease, and prion diseases, with a particular focus on similarities and differences among these syndromes [3].
• Many neurodegenerative diseases, including tauopathies, Parkinson's disease, amyotrophic lateral sclerosis, and the polyglutamine diseases, are characterized by intracellular aggregation of pathogenic proteins [4].
• In particular, they review evidence suggesting a possible involvement of oxidative alterations of glutamate transporters in specific pathologies, including amyotrophic lateral sclerosis, Alzheimer's disease, brain trauma and ischaemia [5].

Psychiatry related information on Amyotrophic Lateral Sclerosis

• This article will review new data in this area, focusing on some major human neurological diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease, Creutzfeldt-Jakob disease, and Alzheimer disease [6].
• A possibility is offered by assessing glutamate levels in biological fluid, such as plasma and CSF, where increased levels of this amino acid have been reported in patients affected by stroke, amyotrophic lateral sclerosis (ALS), and AIDS dementia complex [7].
• These processes of degenerative loss of motor neurons and proliferation of reactive astrocytes with increased levels of fragmented GFAP in the Mnd spinal cord during development seem to be characteristic and preceded the deterioration of motor activities in this animal model of amyotrophic lateral sclerosis [8].
• We speculate that sleep disorders with hypopneas and O2 desaturation episodes were the initial symptoms of amyotrophic lateral sclerosis [9].
• CONCLUSIONS: The feasibility, psychometric, and interpretive findings support the validity of the Sickness Impact Profile for assessing outcomes of amyotrophic lateral sclerosis and its treatment [10].

High impact information on Amyotrophic Lateral Sclerosis

• Over 100 different mutations have been identified in the sod1 genes of patients diagnosed with the familial form of amyotrophic lateral sclerosis (fALS) [11].
• Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis [11].
• ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis [1].
• We identified the missense mutation L967Q in Vps54 in the wobbler mouse, an animal model of amyotrophic lateral sclerosis, and also characterized a lethal allele, Vps54(beta-geo) [12].
• VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death [13].

Chemical compound and disease context of Amyotrophic Lateral Sclerosis

• Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis [14].
• Riluzole in amyotrophic lateral sclerosis [15].
• The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis [16].
• Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis [17].
• Because the above-mentioned factors are important in amyotrophic lateral sclerosis (ALS), we tested minocycline in mice with ALS [18].

Biological context of Amyotrophic Lateral Sclerosis

• Ciliary neurotrophic factor (CNTF) has been shown in various rodent models to reduce the motor neuron cell death similar to that seen in amyotrophic lateral sclerosis (ALS) [19].
• Genotyping and linkage analyses demonstrated that this infantile-onset ascending hereditary spastic paralysis (IAHSP) is allelic to the condition previously reported as juvenile amyotrophic lateral sclerosis at the ALS2 locus on chromosome 2q33-35 (LOD score 6.66 at recombination fraction 0) [20].
• The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis [21].
• The pathogenesis of cell death in amyotrophic lateral sclerosis (ALS) may involve glutamate-mediated excitotoxicity, oxidative damage, and apoptosis [22].
• Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex [23].

Anatomical context of Amyotrophic Lateral Sclerosis

• Glial cells increase nerve growth factor (NGF) expression in neuropathological conditions, and the sensory system can be affected in the amyotrophic lateral sclerosis (ALS) type of motor neuronic disease [24].
• Pulmonary effects of thyrotropin-releasing hormone in amyotrophic lateral sclerosis [25].
• Concentrations of glutamic acid have been reported to be elevated in fasting plasma and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS); glycine concentrations have also been reported to be increased in the CSF of such patients [26].
• Recent studies provided evidence for a generalized defect in glutamate metabolism in patients with amyotrophic lateral sclerosis, associated with widespread alterations in the central nervous system levels of this excitatory amino acid putative transmitter [27].
• Deficient glutamate transport has been identified in the motor cortex and the spinal cord of tissue from amyotrophic lateral sclerosis (ALS) patients [23].

Gene context of Amyotrophic Lateral Sclerosis

• We report here such deregulation of Cdk5 activity associated with the hyperphosphorylation of tau and neurofilament (NF) proteins in mice expressing a mutant superoxide dismutase (SOD1(G37R)) linked to amyotrophic lateral sclerosis (ALS) [28].
• Mutation-induced aggregation of the dimeric enzyme Cu, Zn superoxide dismutase 1 (SOD1) has been implicated in the familial form of the disease amyotrophic lateral sclerosis, but the mechanism of aggregation is not known [29].
• In addition, patients with sporadic amyotrophic lateral sclerosis who had a homozygous CNTF gene defect showed significantly earlier disease onset but did not show a significant difference in disease duration [30].
• Familial amyotrophic lateral sclerosis (FALS) is associated with mutations in SOD1, the gene encoding copper/zinc superoxide dismutase (CuZnSOD) [31].
• Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL [32].

Analytical, diagnostic and therapeutic context of Amyotrophic Lateral Sclerosis

• Cell culture evidence for neuronal degeneration in amyotrophic lateral sclerosis being linked to glutamate AMPA/kainate receptors [33].
• Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis [34].
• Using transcranial magnetic stimulation, the effect of riluzole (RLZ) on cortical excitability was studied in patients with amyotrophic lateral sclerosis (ALS) [35].
• Furthermore, based on immunoprecipitation assays, amyotrophic lateral sclerosis sera were totally negative for antibodies against L-type calcium channels from skeletal muscle or brain [36].
• Gene therapy for amyotrophic lateral sclerosis (ALS) using a polymer encapsulated xenogenic cell line engineered to secrete hCNTF [37].

References