Genetic findings in Parkinson's disease and translation into treatment: a leading role for mitochondria?
Genetic findings in Parkinson's disease and translation into treatment: a leading role for mitochondria?
复制标题
DOI：
10.1111/j.1601-183x.2007.00342.x
复制
发表时间：
2008-03
影响因子：
2.5
通讯作者：
van Broeckhoven, C.
中科院分区：
文献类型：
--
作者：
Bogaerts, V.;Theuns, J.;van Broeckhoven, C.
关键词：
帕金森病（PD）是一种进行性神经退行性运动障碍，在大多数患者中，其病因仍不清楚。在家族性疾病中的分子遗传学研究确定了参与PD发病机制的关键蛋白，并支持线粒体功能障碍的主要作用，这对常见的散发性PD也具有重要意义。虽然目前的治疗暂时缓解症状，但它们不能阻止疾病的进展。因此，靶向PD发病机制（包括线粒体功能障碍）的潜在途径的药物对PD的神经保护具有很大的希望。在这里，我们总结了通过遗传研究鉴定的蛋白质（α-突触核蛋白，parkin，PINK 1，DJ-1，LRRK 2和HTRA 2）如何适应并增加我们目前对线粒体功能障碍在PD中的作用的理解。我们强调这些遗传学发现如何为我们提供合适的动物模型，并批判性地回顾所获得的见解将如何有助于更好地治疗PD。
Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder and in most patients its aetiology remains unknown. Molecular genetic studies in familial forms of the disease identified key proteins involved in PD pathogenesis, and support a major role for mitochondrial dysfunction, which is also of significant importance to the common sporadic forms of PD. While current treatments temporarily alleviate symptoms, they do not halt disease progression. Drugs that target the underlying pathways to PD pathogenesis, including mitochondrial dysfunction, therefore hold great promise for neuroprotection in PD. Here we summarize how the proteins identified through genetic research (α-synuclein, parkin, PINK1, DJ-1, LRRK2 and HTRA2) fit into and add to our current understanding of the role of mitochondrial dysfunction in PD. We highlight how these genetic findings provided us with suitable animal models and critically review how the gained insights will contribute to better therapies for PD.