Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons

Doucet-Beaupre Helene; Gilbert Catherine; Profes Marcos SchaanChabrat AudreyPacelli ConsigliaGiguere NicolasRioux VeroniqueCharest JulienDeng QiaolinLaguna AriadnaEricson JohanPerlmann ThomasAng Siew-LanCicchetti FrancescaParent MartinTrudeau Louis-EricLevesque Martin

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Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons

机译：Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons

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The LIM-homeodomain transcription factors Lmx1a and Lmx1b play critical roles during the development of midbrain dopaminergic progenitors, but their functions in the adult brain remain poorly understood. We show here that sustained expression of Lmx1a and Lmx1b is required for the survival of adult midbrain dopaminergic neurons. Strikingly, inactivation of Lmx1a and Lmx1b recreates cellular features observed in Parkinson's disease. We found that Lmx1a/b control the expression of key genes involved in mitochondrial functions, and their ablation results in impaired respiratory chain activity, increased oxidative stress, and mitochondrial DNA damage. Lmx1a/b deficiency caused axonal pathology characterized by alpha-synuclein(+) inclusions, followed by a progressive loss of dopaminergic neurons. These results reveal the key role of these transcription factors beyond the early developmental stages and provide mechanistic links between mitochondrial dysfunctions, alpha-synuclein aggregation, and the survival of dopaminergic neurons.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2016年第30期|E4387-E4396|共10页
作者
Doucet-Beaupre Helene; Gilbert Catherine; Profes Marcos SchaanChabrat AudreyPacelli ConsigliaGiguere NicolasRioux VeroniqueCharest JulienDeng QiaolinLaguna AriadnaEricson JohanPerlmann ThomasAng Siew-LanCicchetti FrancescaParent MartinTrudeau Louis-EricLevesque Martin;
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作者单位

Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden;

Univ Laval, Fac Med, Dept Psychiat & Neurosci, Quebec City, PQ G1V 0A6, Canada;

Francis Crick Inst, London NW1 2BE, EnglandUniv Montreal, Fac Med, Cent Nervous Syst Res Grp, Dept Pharmacol, Montreal, PQ H3T 1J4, Canada;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
transcription factors; Parkinson's disease; mitochondrial dysfunctions; protein aggregates; dopamine neurons;

Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons

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