期刊
DISEASE MODELS & MECHANISMS
卷 4, 期 2, 页码 193-U72出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dmm.006833
关键词
-
资金
- Wellcome Trust [081958/2/07/Z, WT082366MA]
- European Union
- Medical Research Council [G0401641]
- MRC [G0401641] Funding Source: UKRI
- Medical Research Council [G0401641] Funding Source: researchfish
Axon degeneration is observed in neurodegenerative diseases and neuroinflammatory disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis. The molecular basis of this process remains largely unknown. Here, we show that mice deleted for the tumour suppressor LKB1 (also called STK11) in the spinal cord, some parts of the brain and in the endocrine pancreas (beta LKB1KO mice) develop hind-limb dysfunction and axon degeneration at about 7 weeks. Demyelination and macrophage infiltration are observed in the white matter of these mice, predominantly in the bilateral and anterior funiculi of the thoracic segment of the spinal cord, suggesting damage to the ascending sensory signalling pathway owing to LKB1 deletion in the brain. Microtubule structures were also affected in the degenerated foci, with diminished neurofilament and tubulin expression. Deletion of both PRKAA1 genes, whose products AMPK alpha 1 and AMPK alpha 2 are also downstream targets of LKB1, with the same strategy was without effect. We thus define LKB1 as an intrinsic suppressor of axon degeneration and a possible target for strategies that can reverse this process.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据