Mitochondrial iron-sulfur cluster dysfunction in neurodegenerative disease.
Mitochondrial iron-sulfur cluster dysfunction in neurodegenerative disease.
复制标题
DOI：
10.3389/fphar.2014.00029
复制
发表时间：
2014
影响因子：
5.6
通讯作者：
Isaya G
中科院分区：
文献类型：
--
作者：
Isaya G
越来越多的证据支持线粒体铁代谢在神经退行性疾病（如弗里德赖希共济失调（FRDA）和帕金森病（PD））的病理生理以及与衰老过程相关的运动和认知衰退中发挥作用。铁硫酶缺陷和区域铁积累已在这些条件下观察到。尽管FRDA和PD之间存在显著的病因学、临床和病理差异，但线粒体铁硫团簇（ISCs）生物发生缺陷可能是导致细胞内铁分布异常的共同潜在机制，包括线粒体铁积累、氧化磷酸化缺陷和神经系统特定区域的氧化应激。此外，类似的机制可能有助于年龄依赖性铁积累发生在某些大脑区域，如苍白球和黑质。靶向螯合铁和活性氧似乎是FRDA和PD以及其他与年龄相关的神经退行性疾病的可能治疗选择。然而，需要研究人类ISC合成的新技术来(i)评估这一途径中的缺陷如何促进神经退行性疾病的自然史，以及（ii）在疾病过程的早期，在它们引起不可逆的神经元细胞损伤之前，开发治疗方法来纠正这些缺陷。
Growing evidence supports a role for mitochondrial iron metabolism in the pathophysiology of neurodegenerative disorders such as Friedreich ataxia (FRDA) and Parkinson disease (PD) as well as in the motor and cognitive decline associated with the aging process. Iron–sulfur enzyme deficits and regional iron accumulation have been observed in each of these conditions. In spite of significant etiological, clinical and pathological differences that exist between FRDA and PD, it is possible that defects in mitochondrial iron–sulfur clusters (ISCs) biogenesis represent a common underlying mechanism leading to abnormal intracellular iron distribution with mitochondrial iron accumulation, oxidative phosphorylation deficits and oxidative stress in susceptible cells and specific regions of the nervous system. Moreover, a similar mechanism may contribute to the age-dependent iron accumulation that occurs in certain brain regions such as the globus pallidus and the substantia nigra. Targeting chelatable iron and reactive oxygen species appear as possible therapeutic options for FRDA and PD, and possibly other age-related neurodegenerative conditions. However, new technology to interrogate ISC synthesis in humans is needed to (i) assess how defects in this pathway contribute to the natural history of neurodegenerative disorders and (ii) develop treatments to correct those defects early in the disease process, before they cause irreversible neuronal cell damage.
登录
查看更多内容
影响因子：
--
作者：
Barton, James C
通讯作者：
Barton, James C
Frataxin缺乏症的功能基因组分析揭示了组织特异性的改变，并将PPARGAMMA途径鉴定为弗里德里希共济失调的治疗靶标。
影响因子：
3.5
作者：
Coppola G;Marmolino D;Lu D;Wang Q;Cnop M;Rai M;Acquaviva F;Cocozza S;Pandolfo M;Geschwind DH
通讯作者：
Geschwind DH
影响因子：
2.9
作者：
Bulteau, AL;Ikeda-Saito, M;Szweda, LI
通讯作者：
Szweda, LI
影响因子：
5.3
作者：
Gerber, J;Neumann, K;Lill, R
通讯作者：
Lill, R
影响因子：
4.8
作者：
Chen, OS;Crisp, RJ;Kaplan, J
通讯作者：
Kaplan, J