'Rejuvenation' protects neurons in mouse models of Parkinson's disease
'Rejuvenation' protects neurons in mouse models of Parkinson's disease
复制标题
DOI：
10.1038/nature05865
复制
发表时间：
2007-06-28
期刊：
影响因子：
64.8
通讯作者：
Surmeier, D. James
中科院分区：
文献类型：
--
作者：
Chan, C. Savio;Guzman, Jaime N.;Surmeier, D. James
为什么大脑黑质的多巴胺神经元在帕金森病中死亡一直是一个持久的谜。我们的研究表明，这些神经元异常依赖L型Ca（v）1.3 Ca 2+通道来驱动其维持的、有节奏的起搏，这使它们容易受到被认为有助于疾病进展的压力源的影响。对这些通道的依赖随着年龄的增长而增加，因为黑质中的幼年多巴胺神经元使用与帕金森病中未受影响的神经元相同的起搏机制。这些机制在成年期仍然是潜伏的，阻断成年神经元中的Ca（v）1.3 Ca2+通道可诱导恢复到幼年形式的起搏。这种阻断（“返老还童”）在帕金森病的体外和体内模型中保护这些神经元，指出了一种可以减缓或阻止疾病进展的新策略。
Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson's disease. These mechanisms remain latent in adulthood, and blocking Ca(v)1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking ('rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease.