Mitochondrial dysfunction in Parkinson's disease - a key disease hallmark with therapeutic potential.

Mitochondrial dysfunction in Parkinson's disease - a key disease hallmark with therapeutic potential.
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DOI:
10.1186/s13024-023-00676-7
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发表时间:
2023-11-11
影响因子:
15.1
通讯作者:
Geibl, Fanni F.
Geibl, Fanni F.
中科院分区:
医学1区
文献类型:
--
作者:
Henrich, Martin T.;Oertel, Wolfgang H.;Surmeier, D. James;Geibl, Fanni F.

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线粒体功能障碍与特发性和遗传性帕金森氏病的病因相关(PD),旨在改善线粒体功能障碍的策略,包括抗氧化剂,包括抗氧化药物,抗氧化药物和钢铁螯合物在疾病中的临床中均未进行。包括对电子传输链复合物1的损害,氧化应激增加,受到干扰线粒体质量控制机制和细胞生物能缺乏。此外,我们在当前的PD发病机理中概述了线粒体的神经变性途径,并审查了过去和当前的治疗策略,以便更好地了解为什么迄今为止翻译工作不成功。
Mitochondrial dysfunction is strongly implicated in the etiology of idiopathic and genetic Parkinson’s disease (PD). However, strategies aimed at ameliorating mitochondrial dysfunction, including antioxidants, antidiabetic drugs, and iron chelators, have failed in disease-modification clinical trials. In this review, we summarize the cellular determinants of mitochondrial dysfunction, including impairment of electron transport chain complex 1, increased oxidative stress, disturbed mitochondrial quality control mechanisms, and cellular bioenergetic deficiency. In addition, we outline mitochondrial pathways to neurodegeneration in the current context of PD pathogenesis, and review past and current treatment strategies in an attempt to better understand why translational efforts thus far have been unsuccessful.
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