Centre Hospitalier Universitaire, Département de Biochimie et Génétique, Angers, France; UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
UMR CNRS 6214-INSERM 1083, Université d'Angers, Angers, France.
Neurobiol Dis. 2016 Jun;90:20-6. doi: 10.1016/j.nbd.2015.08.015. Epub 2015 Aug 23.
Mutations in the Optic Atrophy 1 gene (OPA1) were first identified in 2000 as the main cause of Dominant Optic Atrophy, a disease specifically affecting the retinal ganglion cells and the optic nerve. Since then, an increasing number of symptoms involving the central, peripheral and autonomous nervous systems, with considerable variations of age of onset and severity, have been reported in OPA1 patients. This variety of phenotypes is attributed to differences in the effects of OPA1 mutations, to the mode of inheritance, which may be mono- or bi-allelic, and eventually to somatic mitochondrial DNA mutations. The diversity of the pathophysiological mechanisms involved in OPA1-related disorders is linked to the crucial role played by OPA1 in the maintenance of mitochondrial structure, genome and function. The neurological expression of these disorders highlights the importance of mitochondrial dynamics in neuronal processes such as dendritogenesis, axonal transport, and neuronal survival. Thus, OPA1-related disorders may serve as a paradigm in the wider context of neurodegenerative syndromes, particularly for the development of novel therapeutic strategies against these diseases.
OPA1 基因突变于 2000 年首次被确定为显性视神经萎缩的主要病因，这种疾病专门影响视网膜神经节细胞和视神经。自那时以来，越来越多的涉及中枢、周围和自主神经系统的症状在 OPA1 患者中被报道，其发病年龄和严重程度差异很大。这种表型的多样性归因于 OPA1 突变的影响、遗传模式的差异，可能是单等位基因或双等位基因，最终归因于体细胞线粒体 DNA 突变。OPA1 相关疾病中涉及的病理生理机制的多样性与 OPA1 在维持线粒体结构、基因组和功能方面的关键作用有关。这些疾病的神经表现强调了线粒体动力学在树突发生、轴突运输和神经元存活等神经元过程中的重要性。因此，OPA1 相关疾病可能成为神经退行性综合征更广泛背景下的一个范例，特别是对于开发针对这些疾病的新型治疗策略。
