期刊
NATURE NEUROSCIENCE
卷 19, 期 4, 页码 557-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4257
关键词
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资金
- Jackson Lab Startup Funds [1R21 NS075382-01A1]
- Intramural Research Program of the National Institute on Drug Abuse
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders whose pathogenesis remains largely unknown. Using TDP-43(A315T) mice, an ALS and FTD model with marked cortical pathology, we found that hyperactive somatostatin interneurons disinhibited layer 5 pyramidal neurons (L5-PNs) and contributed to their excitotoxicity. Focal ablation of somatostatin interneurons efficiently restored normal excitability of L5-PNs and alleviated neurodegeneration, suggesting a new therapeutic target for ALS and FTD.
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