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)

The receptor tyrosine kinase RET is part of a functional receptor for glial cell derived neurotrophic factor (GDNF) and neurturin (NTN) which are potent neurotrophic factors for motoneurons. Here, we have studied RET-like immunoreactivity of motoneurons in post-mortem spinal cords of patients with amyotrophic lateral sclerosis (ALS) and in controls. We report that the intensity of RET-like immunostaining of motoneurons in ALS is decreased significantly to 81% of control values. Despite this change, the proportion of all large (>40 micron diameter) motoneurons showing RET-like immunoreactivity in ALS remains high (82-85%) and is not significantly different to controls. The persistence of RET-like immunoreactivity in the majority of large motoneurons in ALS could be important in the design of clinical trials of GDNF and NTN.
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PMID:RET-like immunostaining of spinal motoneurons in amyotrophic lateral sclerosis. 957 3

Degenerative spinal motor diseases, like amyotrophic lateral sclerosis, are produced by progressive degeneration of motoneurons. Their clinical manifestations include a progressive muscular weakness and atrophy, which lead to paralysis and premature death. Current pharmacological therapies fail to stop the progression of motor deficits or to restore motor function. The purpose of our study was to explore the possible beneficial effect of mouse adult hematopoietic stem cells (hSCs) transplanted into the spinal cord of a mouse model of motoneuron degeneration. Our results show that grafted hSCs survive in the spinal cord. In addition, the number of motoneurons in the transplanted spinal cord is larger than in non-transplanted mdf mice at the same spinal cord segments and importantly, motor function significantly improves. These effects can be explained by the increased levels of glial cell line derived neurotrophic factor (GDNF) around host motoneurons produced by the grafted cells. Thus, these experiments demonstrate the neuroprotective effect of adult hSCs in the model employed and indicate that this cell type may contribute to ameliorating motor function in degenerative spinal motor diseases.
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PMID:Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration. 1733 96

Motorneuron degenerative diseases, such as amyotrophic lateral sclerosis (ALS), are characterized by the progressive and rapid loss of motor neurons in the brain and spinal cord, leading to paralysis and death. GDNF (glial cell line derived neurotrophic factor) has been previously shown to be capable of protecting motor-neurons in ALS animal models although its delivery to the spinal cord after systemic administration is blocked by the blood brain barrier. Thus, it is necessary to develop new neurotrophic approaches to protect these motor neurons from death. Bone marrow-derived stem cells have been shown to be capable of improving a large variety of neurodegenerative disorders through neurotrophic mediated mechanisms. Here we analyzed the effect of transplanting whole bone marrow or cultured mesenchymal stem cells into the spinal cord of a motor neuron degenerative mouse model. Motor functions were analyzed using various behavior tests for several weeks after transplantation. We observed that bone marrow, and to a lesser degree mesenchymal stem cell, treated mice improved significantly in the motor tests performed, coinciding with a higher GDNF immunoreactivity in the grafted spinal cord. In several cases, the treated spinal cords were extracted, the engrafted bone marrow cells isolated and cultured, and finally re-transplanted into the spleen of immunodeficient mice. Re-grafted cells were detected in the host spleen, bloodstream and bone marrow, demonstrating a phenotypic stability. Thus, bone marrow cells do not suffer significant phenotypic modifications and is an efficient procedure to ameliorate motor-neuron degeneration, making it a possible therapeutic approach.
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PMID:Comparative effects between bone marrow and mesenchymal stem cell transplantation in GDNF expression and motor function recovery in a motorneuron degenerative mouse model. 2171 32