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)

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the degeneration of the motor neurons. We tested whether treatment of superoxide dismutase (SOD1)-G93A transgenic mouse, a model of ALS, with a neural stem cell subpopulation double positive for Lewis X and the chemokine receptor CXCR4 (LeX+CXCR4+) can modify the disease's progression. In vitro, after exposure to morphogenetic stimuli, LeX+CXCR4+ cells generate cholinergic motor neuron-like cells upon differentiation. LeX+CXCR4+ cells deriving from mice expressing Green Fluorescent Protein in all tissues or only in motor neurons, after a period of priming in vitro, were grafted into spinal cord of SOD1-G93A mice. Transplanted transgenic mice exhibited a delayed disease onset and progression, and survived significantly longer than non-treated animals by 23 days. Examination of the spinal cord revealed integration of donor-derived cells that differentiated mostly in neurons and in a lower proportion in motor neuron-like cells. Quantification of motor neurons of the spinal cord suggests a significant neuroprotection by LeX+CXCR4+ cells. Both VEGF- and IGF1-dependent pathways were significantly modulated in transplanted animals compared to controls, suggesting a role of these neurotrophins in MN protection. Our results support the therapeutic potential of neural stem cell fractions through both neurogenesis and growth factors release in motor neuron disorders.
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PMID:Neural stem cells LewisX+ CXCR4+ modify disease progression in an amyotrophic lateral sclerosis model. 1743 86

In mammalian spinal cords, no neurogenesis has been observed after initial development. However developed mammalian spinal cords seemingly contain neural stem cells (NSC), which can give rise to neurons and glial cells when they are placed in appropriate environments. The purpose of the present paper was to investigate the developing, developed, and diseased human spinal cord to see which cell types have an immunophenotype similar to NSC. In 12 specimens from preterm neonates and term infants up to 14 months old, nestin was expressed in cells that extended fibrous processes and were located around the midline in the ependymal layer. In all the preterm neonates, Musashi-1 and glial fibrillary acidic protein (GFAP) were also expressed in this subpopulation, whereas Lewis X was detected in a less restricted subpopulation. Nestin expression by these cells was not detected in most adult spinal cords, but was observed in three spinal cords from 13 amyotrophic lateral sclerosis patients and eight of 14 spinal cords involved by the tumor. The present observations suggest that during gestation a subpopulation of cells in the ependymal layer remains undifferentiated as potential NSC/neural progenitor cells, and becomes unidentifiable in early infancy. These cells, however, appear in response to disease conditions, especially tumor involvement.
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PMID:Distribution of nestin and other stem cell-related molecules in developing and diseased human spinal cord. 1753 67