Correia Sónia C, Perry George, Moreira Paula I
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
Biochim Biophys Acta. 2016 Oct;1862(10):1909-17. doi: 10.1016/j.bbadis.2016.07.010. Epub 2016 Jul 25.
The vigorous axonal transport of mitochondria, which serves to distribute these organelles in a dynamic and non-uniform fashion, is crucial to fulfill neuronal energetic requirements allowing the maintenance of neurons structure and function. Particularly, axonal transport of mitochondria and their spatial distribution among the synapses are directly correlated with synaptic activity and integrity. Despite the basis of Alzheimer's disease (AD) remains enigmatic, axonal pathology and synaptic dysfunction occur prior the occurrence of amyloid-β (Aβ) deposition and tau aggregation, the two classical hallmarks of this devastating neurodegenerative disease. Importantly, the early stages of AD are marked by defects on axonal transport of mitochondria as denoted by the abnormal accumulation of mitochondria within large swellings along dystrophic and degenerating neuritis. Within this scenario, this review is devoted to identify the molecular "roadblocks" underlying the abnormal axonal transport of mitochondria and consequent synaptic "starvation" and neuronal degeneration in AD. Understanding the molecular nature of defective mitochondrial transport may provide a new avenue to counteract AD pathology.
线粒体的活跃轴突运输以动态且不均匀的方式分布这些细胞器，对于满足神经元的能量需求、维持神经元结构和功能至关重要。特别是，线粒体的轴突运输及其在突触间的空间分布与突触活动和完整性直接相关。尽管阿尔茨海默病（AD）的病因仍不明朗，但轴突病理和突触功能障碍在淀粉样β蛋白（Aβ）沉积和tau蛋白聚集之前就已出现，而这两种现象是这种毁灭性神经退行性疾病的两个经典特征。重要的是，AD的早期阶段以线粒体轴突运输缺陷为特征，表现为线粒体在营养不良和退化神经突的大肿胀内异常积聚。在此背景下，本综述致力于确定AD中线粒体轴突运输异常以及随之而来的突触“饥饿”和神经元退化背后的分子“障碍”。了解线粒体运输缺陷的分子本质可能为对抗AD病理提供新途径。
