期刊
NATURE NEUROSCIENCE
卷 10, 期 5, 页码 615-622出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn1876
关键词
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资金
- NIA NIH HHS [R01 AG021617, AG 21617] Funding Source: Medline
- NIDDK NIH HHS [R01 DK058056, DK58056] Funding Source: Medline
- NIEHS NIH HHS [ES013177, R21 ES013177] Funding Source: Medline
- NINDS NIH HHS [NS38370, P50 NS038370, NS42269, P01 NS011766, R01 NS042269, NS11766] Funding Source: Medline
Mutations in superoxide dismutase-1 ( SOD1) cause a form of the fatal paralytic disorder amyotrophic lateral sclerosis ( ALS), presumably by a combination of cell-autonomous and non - cell- autonomous processes. Here, we show that expression of mutated human SOD1 in primary mouse spinal motor neurons does not provoke motor neuron degeneration. Conversely, rodent astrocytes expressing mutated SOD1 kill spinal primary and embryonic mouse stem cell - derived motor neurons. This is triggered by soluble toxic factor( s) through a Bax- dependent mechanism. However, mutant astrocytes do not cause the death of spinal GABAergic or dorsal root ganglion neurons or of embryonic stem cell - derived interneurons. In contrast to astrocytes, fibroblasts, microglia, cortical neurons and myocytes expressing mutated SOD1 do not cause overt neurotoxicity. These findings indicate that astrocytes may play a role in the specific degeneration of spinal motor neurons in ALS. Identification of the astrocyte- derived soluble factor( s) may have far- reaching implications for ALS from both a pathogenic and therapeutic standpoint.
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