Cai Huaibin, Liu Guoxiang, Sun Lixin, Ding Jinhui
Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892 USA.
Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892 USA.
Transl Neurodegener. 2014 Dec 10;3:27. doi: 10.1186/2047-9158-3-27. eCollection 2014.
A preferential dysfunction/loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) accounts for the main motor symptoms of Parkinson's disease (PD), the most common degenerative movement disorder. However, the neuronal loss is not stochastic, but rather displays regionally selectivity, indicating the existence of different DA subpopulations in the SNpc. To identify the underlying molecular determinants is thereby instrumental in understanding the pathophysiological mechanisms of PD-related neuron dysfunction/loss and offering new therapeutic targets. Recently, we have demonstrated that aldehyde dehydrogenase 1 (ALDH1A1) is one such molecular determinant that defines and protects an SNpc DA neuron subpopulation preferentially affected in PD. In this review, we provide further analysis and discussion on the roles of ALDH1A1 in the function and survival of SNpc DA neurons in both rodent and human brains. We also explore the feasibility of ALDH1A1 as a potential biomarker and therapeutic target for PD.
黑质致密部（SNpc）中多巴胺能（DA）神经元的优先功能障碍/丧失是帕金森病（PD）主要运动症状的原因，帕金森病是最常见的退行性运动障碍。然而，神经元的丧失并非随机发生，而是表现出区域选择性，这表明SNpc中存在不同的DA亚群。因此，确定潜在的分子决定因素有助于理解与PD相关的神经元功能障碍/丧失的病理生理机制，并提供新的治疗靶点。最近，我们已经证明醛脱氢酶1（ALDH1A1）就是这样一种分子决定因素，它定义并保护在PD中优先受影响的SNpc DA神经元亚群。在这篇综述中，我们对ALDH1A1在啮齿动物和人类大脑中SNpc DA神经元的功能和存活中的作用进行了进一步的分析和讨论。我们还探讨了ALDH1A1作为PD潜在生物标志物和治疗靶点的可行性。
