Trypanosome prereplication machinery: a potential new target for an old problem.
Trypanosome prereplication machinery: a potential new target for an old problem.
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DOI：
10.4061/2011/518258
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Elias MC
中科院分区：
文献类型：
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作者：
Calderano SG;de Melo Godoy PD;da Cunha JP;Elias MC
全世界约有1000万人患有由克氏锥虫引起的恰加斯病，疾病负担主要集中在拉丁美洲。昏睡病是另一个严重的健康问题，由布氏锥虫引起，尤其在撒哈拉以南的国家。不幸的是，目前用于治疗这些疾病的药物具有毒性作用，并且对所有疾病阶段或寄生虫菌株并非都有效。因此，显然需要开发新的药物和药物靶点来治疗这些疾病。我们提出锥虫的复制前机制组分Orc1/Cdc6可作为药物开发的一个潜在靶点。在锥虫中，Orc1/Cdc6参与核DNA复制，并且尽管它参与这样一个保守的过程，但Orc1/Cdc6不同于哺乳动物的Orc1和Cdc6蛋白。此外，在布氏锥虫中通过RNA干扰介导的锥虫Orc1/Cdc6表达沉默降低了细胞存活率，这表明Orc1/Cdc6对锥虫的生存至关重要。
Approximately ten million people suffer from Chagas disease worldwide, caused by Trypanosoma cruzi, with the disease burden predominately focused in Latin America. Sleeping sickness is another serious health problem, caused by Trypanosoma brucei, especially in sub-Saharan countries. Unfortunately, the drugs currently available to treat these diseases have toxic effects and are not effective against all disease phases or parasite strains. Therefore, there is a clear need for the development of novel drugs and drug targets to treat these diseases. We propose the trypanosome prereplication machinery component, Orc1/Cdc6, as a potential target for drug development. In trypanosomes, Orc1/Cdc6 is involved in nuclear DNA replication, and, despite its involvement in such a conserved process, Orc1/Cdc6 is distinct from mammalian Orc1 and Cdc6 proteins. Moreover, RNAi-mediated silencing of trypanosome Orc1/Cdc6 expression in T. brucei decreased cell survival, indicating that Orc1/Cdc6 is critical for trypanosome survival.