The immune system as a driver of mitochondrial disease pathogenesis: a review of evidence.
The immune system as a driver of mitochondrial disease pathogenesis: a review of evidence.
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DOI：
10.1186/s13023-022-02495-3
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发表时间：
2022-09-02
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
遗传性线粒体疾病对人类健康构成重大挑战。这些疾病在临床表现和遗传起源上具有极大的异质性，并且通常涉及具有严重进行性症状的多系统疾病。线粒体疾病是遗传性代谢紊乱的最常见原因，也是遗传性神经系统疾病的最常见原因之一，但尚无经过验证的治疗策略。线粒体疾病发病机制的基本细胞和分子机制尚未得到解决，这阻碍了开发治疗药物的努力。在最近的临床前工作中，我们已经表明，针对免疫系统的药物可以预防Leigh综合征的Ndufs4（KO）模型中的疾病，这表明免疫系统至少在这种形式的线粒体疾病的发病机制中起着因果作用。有趣的是，许多病例报告表明免疫靶向治疗可能对遗传性线粒体疾病有益。在这里，我们总结了临床和临床前证据，表明免疫系统在介导至少某些形式的遗传性线粒体疾病的发病机制中发挥着关键作用。重要的临床和临床前证据表明，免疫系统在至少某些形式的遗传性线粒体疾病的发病机制中发挥着重要作用。
Genetic mitochondrial diseases represent a significant challenge to human health. These diseases are extraordinarily heterogeneous in clinical presentation and genetic origin, and often involve multi-system disease with severe progressive symptoms. Mitochondrial diseases represent the most common cause of inherited metabolic disorders and one of the most common causes of inherited neurologic diseases, yet no proven therapeutic strategies yet exist. The basic cell and molecular mechanisms underlying the pathogenesis of mitochondrial diseases have not been resolved, hampering efforts to develop therapeutic agents. In recent pre-clinical work, we have shown that pharmacologic agents targeting the immune system can prevent disease in the Ndufs4(KO) model of Leigh syndrome, indicating that the immune system plays a causal role in the pathogenesis of at least this form of mitochondrial disease. Intriguingly, a number of case reports have indicated that immune-targeting therapeutics may be beneficial in the setting of genetic mitochondrial disease. Here, we summarize clinical and pre-clinical evidence suggesting a key role for the immune system in mediating the pathogenesis of at least some forms of genetic mitochondrial disease. Significant clinical and pre-clinical evidence indicates a key role for the immune system as a significant in the pathogenesis of at least some forms of genetic mitochondrial disease.
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影响因子：
3.7
作者：
Clarke SL;Bowron A;Gonzalez IL;Groves SJ;Newbury-Ecob R;Clayton N;Martin RP;Tsai-Goodman B;Garratt V;Ashworth M;Bowen VM;McCurdy KR;Damin MK;Spencer CT;Toth MJ;Kelley RI;Steward CG
通讯作者：
Steward CG
影响因子：
7.3
作者：
Alston, Charlotte L.;Rocha, Mariana C.;Lax, Nichola Z.;Turnbull, Doug M.;Taylor, Robert W.
通讯作者：
Taylor, Robert W.
影响因子：
4
作者：
Bindu, Parayil Sankaran;Sonam, Kothari;Taly, Arun B.
通讯作者：
Taly, Arun B.
影响因子：
2
作者：
Edgerley, Katharine;Barnicoat, Angela;Smithson, Sarah F.
通讯作者：
Smithson, Sarah F.
影响因子：
3.8
作者：
Eom, Soyong;Lee, Ha Neul;Lee, Young-Mock
通讯作者：
Lee, Young-Mock