Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets?
Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets?
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DOI：
10.1007/s10863-014-9576-6
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发表时间：
2015-04
影响因子：
3
通讯作者：
Duchen, Michael R.
中科院分区：
文献类型：
--
作者：
Corona, Juan Carlos;Duchen, Michael R.
细胞的线粒体群体的持续完整性对于维持细胞健康至关重要，并且该完整性的破坏与人类疾病，特别是神经退行性疾病密切相关。这些疾病令人震惊，造成难以形容的痛苦，而治疗却严重不足。因此，了解扰乱线粒体稳态的机制可能是识别潜在新治疗途径的关键。引起线粒体功能障碍的机制包括由线粒体渗透性转换孔（mPTP）的打开引起的急性灾难性功能丧失，其破坏生物能量功能并引发细胞死亡。这在缺血再灌注损伤中表现得最好，尽管它也可能导致许多其他疾病。线粒体稳态的更隐蔽的紊乱可能是由于促进线粒体修复（生物发生）的途径和去除功能障碍的线粒体（线粒体自噬）的途径中的平衡受损。这些过程之间的协调受损正在成为许多神经退行性疾病和神经肌肉疾病的关键特征。在这里，我们审查的途径，可能被证明是有价值的潜在的治疗目标，集中在管理这些过程的协调和参与神经退行性疾病的分子机制。
The sustained integrity of the mitochondrial population of a cell is critical for maintained cell health, and disruption of that integrity is linked strongly to human disease, especially to the neurodegenerative diseases. These are appalling diseases causing untold levels of suffering for which treatment is woefully inadequate. Understanding the mechanisms that disturb mitochondrial homeostasis may therefore prove key to identification of potential new therapeutic pathways. Mechanisms causing mitochondrial dysfunction include the acute catastrophic loss of function caused by opening of the mitochondrial permeability transition pore (mPTP), which collapses bioenergetic function and initiates cell death. This is best characterised in ischaemic reperfusion injury, although it may also contribute to a number of other diseases. More insidious disturbances of mitochondrial homeostasis may result from impaired balance in the pathways that promote mitochondrial repair (biogenesis) and pathways that remove dysfunctional mitochondria (mitophagy). Impaired coordination between these processes is emerging as a key feature of a number of neurodegenerative and neuromuscular disorders. Here we review pathways that may prove to be valuable potential therapeutic targets, focussing on the molecular mechanisms that govern the coordination of these processes and their involvement in neurodegenerative diseases.
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影响因子：
29
作者：
Da Cruz S;Parone PA;Lopes VS;Lillo C;McAlonis-Downes M;Lee SK;Vetto AP;Petrosyan S;Marsala M;Murphy AN;Williams DS;Spiegelman BM;Cleveland DW
通讯作者：
Cleveland DW
影响因子：
3.7
作者：
Clark J;Silvaggi JM;Kiselak T;Zheng K;Clore EL;Dai Y;Bass CE;Simon DK
通讯作者：
Simon DK
影响因子：
64.8
作者：
Fimia, Gian Maria;Stoykova, Anastassia;Cecconi, Francesco
通讯作者：
Cecconi, Francesco
影响因子：
5.3
作者：
Abramov, AY;Canevari, L;Duchen, MR
通讯作者：
Duchen, MR
DOI：
10.1073/pnas.0708959104
发表时间：
2007-11-13
影响因子：
11.1
作者：
Abramov, Andrey Y.;Fraley, Cresson;Pavlov, Evgeny
通讯作者：
Pavlov, Evgeny