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)

To investigate cytokine/chemokine changes in amyotrophic lateral sclerosis (ALS), we simultaneously measured 16 cytokine/chemokines (interleukin [IL]-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 [p70], IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony stimulating factor [G-CSF], macrophage chemoattractant protein-1 [MCP-1], and macrophage inflammatory protein-1beta) in cerebrospinal fluid (CSF) and sera from 37 patients with sporadic ALS and 33 controls using a multiplexed fluorescent bead-based immunoassay. We also conducted immunohistochemical analyses from 8 autopsied ALS cases and 6 nonneurologic disease controls as well as cell culture analyses of relevant cytokines and their receptors. We found that concentrations of G-CSF and MCP-1 were significantly increased in ALS CSF compared with controls. In spinal cords, G-CSF was expressed in reactive astrocytes in ALS cases but not controls, whereas G-CSF receptor expression was significantly decreased in motor neurons of spinal cords from ALS cases. Biologically, G-CSF had a protective effect on the NSC34 cell line under conditions of both oxidative and nutritional stress. We suggested that G-CSF has potentially neuroprotective effects on motor neurons in ALS and that downregulation of its receptor might contribute to ALS pathogenesis. On the other hand, MCP-1 correlated with disease severity, which may aggravate motor neuron damage.
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PMID:Intrathecal upregulation of granulocyte colony stimulating factor and its neuroprotective actions on motor neurons in amyotrophic lateral sclerosis. 1689 15

This study includes three aspects: (1) we have reported some novel or rare mutations of SOD1 (Cu/Zn superoxide dismutase) gene in Chinese families of ALS/MND, and found quite different features from Western patients in polymorphisms with some candidate genes such as vascular endothelial growth factor (VEGF) in sporadic ALS/MND in China. Meanwhile, we have so for established a complete clinical database with more than 1 200 cases; (2) we have established some neurophysiologic techniques of diagnosis and differential diagnosis at early-stage for ALS/MND, which include trigemino-cervical response, sternocleidomastoid and rectus electromyography, contact heat evoked potentials, and motor unit number estimate; (3) we have attempted some experimental and clinical treatments for ALS/MND, which include gene and stem cell therapies in animal models, and a pilot clinical trial of granulocyte colony stimulating factor (G-CSF) for ALS/MND patients (NCT00397423).
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PMID:[Basic and clinical researches on amyotrophic lateral sclerosis/motor neuron disease]. 1972 8

We investigated the safety and efficacy of the granulocyte colony stimulating factor (G-CSF) in 13 patients with amyotrophic lateral sclerosis (ALS). Five-day administration of 2 microg/kg once a day was followed by a six-month observation period. The primary and secondary endpoints were the changes of ALS functional rating scale (ALSFRS) and the compound muscle action potential (CMAP) amplitude, respectively. We found that the declines of ALSFRS and CMAP amplitude after G-CSF administration were significantly less than those measured prior to the treatment. The results suggest G-CSF is safe in ALS patients, and may affect the rate of motor decline.
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PMID:Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis. 1992 35

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motoneurons which progresses differentially in males and females for unknown reason. Here we measured gender differences in pre- and post-synaptic parameters of the neuromuscular transmission in a mutant G93A-SOD1 mouse model of ALS. Using intracellular microelectrode technique we recorded miniature and evoked end-plate potentials (MEPPs and EPPs) in the diaphragm muscle of G93A-SOD1 mice at early symptomatic stage. While no evident alterations in the amplitude of MEPPs was observed in male or female G93A-SOD1 mice, G93A-SOD1 mice displayed dramatically reduced probability of spontaneous acetylcholine release. In contrast, the EPPs evoked by single nerve stimulation had unchanged amplitude and quantal content. In males, but not females, this was accompanied by reduced readily releasable transmitter pool. Transmitter release in both sexes was sensitive to the inhibitory action of reactive oxygen species (ROS), but the production of ROS was increased in the spinal cords of male but not female G93A-SOD1 mice. Treatment with granulocyte colony stimulating factor (GCSF), which we previously found to be beneficial in males, attenuated the increased ROS production indicating involvement of the antioxidant mechanisms and improved ALS-induced synaptic dysfunctions only in males being ineffective in females. Consistent with our findings at synaptic level, GCSF did not change the survival rate or motor performance of female ALS mice. In summary, neuromuscular transmission in ALS mice is impaired at early symptomatic stage when a dramatic presynaptic decline of spontaneous release occurs. Beneficial effects of GCSF treatment on survival in males may be explained by GCSF-improved presynaptic functions in male G93A-SOD1 mice. Development of efficient treatment strategies for ALS may need to be directed in a gender-specific manner.
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PMID:Gender-Specific Mechanism of Synaptic Impairment and Its Prevention by GCSF in a Mouse Model of ALS. 2218 Jul 38

Hematopoietic failure (HF) has been observed in trauma hemorrhagic shock (T/HS) patients. Multiple factors are involved. Elevated serum levels of cytokines, catecholamine, granulocyte colony stimulating factor, peripheral blood hematopoietic progenitor cells (HPCs) and decreased expression of erythropoietin receptor are associated with HF among T/HS. HF leads to anaemia, susceptibility to infection, sepsis and multi-organ failure. There is a lack of molecular understanding of HF and its potential therapeutic strategies. Cell-based therapy has ability to modulate the production of inflammatory cytokines, vascular dysfunction, tissue damage and apoptosis. Human-induced pluripotent stem cells (iPSC) derived HPCs may have the ability to restore HF in T/HS. Autologous cell-based iPSC have great promises for various diseases such as Alzheimer's disease, Parkinson's disease, cardiovascular disease, diabetes, amyotrophic lateral sclerosis, and spinal cord injury without ethical concerns. Similarly, treatment with iPSC derived hematopoietic stem cells can used for the treatment of HF among T/HS and may also improve the outcome. Here, we review the potential of human iPSC derived HSC to reversed HF following T/HS.
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PMID:Human-induced pluripotent stem cells derived hematopoietic progenitor cells for treatment of hematopoietic failure among trauma hemorrhagic shock patients. 3082 91