Mitochondrial Dysfunction in Huntington's Disease
Mitochondrial Dysfunction in Huntington's Disease
复制标题
DOI：
10.1007/978-3-319-71779-1_3
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Cristina Rego, A.
中科院分区：
文献类型：
--
作者：
Carmo, Catarina;Naia, Luana;Cristina Rego, A.
线粒体功能障碍被描述为亨廷顿病(HD)发生选择性神经变性的早期病理机制，HD是一种多谷氨酰胺扩张性疾病，主要影响纹状体和大脑皮层。多年来，线粒体在真核细胞(如神经元)中的作用与经典的细胞动力源大相径庭；事实上，线粒体不仅有助于合成几种代谢物，而且是动态的细胞器，可以分段和融合以实现最大的生物能量性能，沿着微管运输，通过与内质网的相互作用调节细胞内钙稳态，产生自由基并参与细胞死亡过程。事实上，这些活动中的大多数已经被证明在HD中受到影响，潜在地导致了症状前期的神经元功能障碍。本章回顾了线粒体作为受HD影响的神经元的主要调节细胞器的一些证据，揭示了一些潜在的基于线粒体的治疗相关靶点。
Mitochondrial dysfunction has been described as an early pathological mechanism delineating the selective neurodegeneration that occurs in Huntington's disease (HD), a polyglutamine-expansion disorder that largely affects the striatum and the cerebral cortex. Over the years, mitochondria roles in eukaryotic cells (e.g. in neurons) have largely diverged from the classically attributed cell power source; indeed, mitochondria not only contribute for synthesis of several metabolites, but are also dynamic organelles that fragment and fuse to achieve a maximal bioenergetic performance, are transported along microtubules, regulate intracellular calcium homeostasis through the interaction with the endoplasmic reticulum, produce free radicals and participate in cell death processes. Indeed, most of these activities have been demonstrated to be affected in HD, potentially contributing for the neuronal dysfunction in pre-symptomatic stages. This chapter resumes some of the evidences that pose mitochondria as a main regulatory organelle in HD-affected neurons, uncovering some potentially therapeutic mitochondrial-based relevant targets.