期刊
METABOLIC BRAIN DISEASE
卷 30, 期 6, 页码 1369-1377出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11011-015-9706-9
关键词
Amyotrophic lateral sclerosis; hSOD1(G93A); CatWalk; Locomotor activity; AMP kinase; Metabolism
资金
- National Fund for Scientific Research (FNRS, Belgium) [1.5.085.10.F, 1.A198.08]
- Association belge pour les maladies neuromusculaires (ABMM)
- Ministry of Scientific Policy (Belgium) [ARC 10/15-026]
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motoneurons. While the principal cause of the disease remains so far unknown, the onset and progression of the pathology are increasingly associated with alterations in the control of cell metabolism. On the basis of the well-known key roles of 5'-adenosine monophosphate-activated protein kinase (AMPK) in sensing and regulating the intracellular energy status, we hypothesized that mice with a genetic deletion of AMPK would develop locomotor abnormalities that bear similarity with those detected in the very early disease stage of mice carrying the ALS-associated mutated gene hSOD1(G93A). Using an automated gait analysis system (CatWalk), we here show that hSOD1(G93A) mice and age-matched mice lacking the neuronal and skeletal muscle predominant alpha 2 catalytic subunit of AMPK showed an altered gait, clearly different from wild type control mice. Double mutant mice lacking AMPK alpha 2 and carrying hSOD1(G93A) showed the same early gait abnormalities as hSOD1(G93A) mice over an age span of 8 to 16 weeks. Taken together, these data support the concept that altered AMPK function and associated bioenergetic abnormalities could constitute an important component in the early pathogenesis of ALS. Therapeutic interventions acting on metabolic pathways could prove beneficial on early locomotor deficits, which are sensitively detectable in rodent models using the CatWalk system.
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