Mitochondrial dynamics and neurodegeneration.

Mitochondrial dynamics and neurodegeneration.
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DOI:
10.1007/s11910-009-0032-7
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发表时间:
2009-05
影响因子:
5.6
通讯作者:
Lu, Bingwei
Lu, Bingwei
中科院分区:
医学2区
文献类型:
--
作者:
Lu, Bingwei

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线粒体是真核细胞中的关键细胞器,它不仅产生三磷酸腺苷,而且还具有重要的功能,如主持必要的生物合成途径、钙缓冲和细胞凋亡信号。在体内,线粒体通过分裂和融合形成动态网络,经历频繁的形态变化。在神经元中,线粒体分裂/融合的失衡会影响神经元的生理功能,如突触传递和可塑性,并影响神经元的存活。通过对模式生物的遗传学研究,已经确定了线粒体分裂/融合机制的核心组件。人类这些基因中的一些突变被认为与罕见的神经退行性疾病有关,例如夏科-玛丽-牙齿亚型2A型和常染色体显性遗传性视神经萎缩。最近的研究还表明,线粒体的异常分裂/融合与帕金森病等更常见的神经退行性疾病的发病机制有关。这些研究确立了线粒体动力学作为神经退行性疾病研究的新范式。调节线粒体分裂/融合的化合物在疾病干预方面可能具有治疗价值。
Mitochondria are key organelles in eukaryotic cells that not only generate adenosine triphosphate but also perform such critical functions as hosting essential biosynthetic pathways, calcium buffering, and apoptotic signaling. In vivo, mitochondria form dynamic networks that undergo frequent morphologic changes through fission and fusion. In neurons, the imbalance of mitochondrial fission/fusion can influence neuronal physiology, such as synaptic transmission and plasticity, and affect neuronal survival. Core components of the mitochondrial fission/fusion machinery have been identified through genetic studies in model organisms. Mutations in some of these genes in humans have been linked to rare neurodegenerative diseases such as Charcot-Marie-Tooth subtype 2A and autosomal dominant optic atrophy. Recent studies also have implicated aberrant mitochondrial fission/fusion in the pathogenesis of more common neurodegenerative diseases such as Parkinson’s disease. These studies establish mitochondrial dynamics as a new paradigm for neurodegenerative disease research. Compounds that modulate mitochondrial fission/fusion could have therapeutic value in disease intervention.
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