Kinetoplast DNA: A Promising Drug Target for Treatment of Leishmaniasis

Authors

Faridnia, Roghiyeh PhD Student in Parasitology, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

Akhtari, Javad Associate Professor, Department of Medical Nanotechnology, Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran

Fakhar, Mahdi Associate Professor, Department of Parasitology, Toxoplasmosis Research Center, Iranian National Registry Center for Lophomoniasis (INRCL), Mazandaran Branch, Mazandaran University of Medical Sciences, Sari, Iran

Keighobadi, Masoud 4Assistant Professor, Toxoplasmosis Research Center, Iranian National Registry Center for Hydatid Cyst, Mazandaran Branch, Mazandaran University of Medical Sciences, Sari, Iran

Kialashaki, Elham PhD Student in Parasitology, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

Abstract:

Leishmaniasis is a vector-borne zoonotic disease caused by various species of the genus Leishmania, (trypanosomatidae family) that is transmitted by phlebotomine sandflies. The disease can present in a range of clinical forms, including dermal lesions, metastasis mucocutaneous forms, and fatal visceral forms. In this non-systematic review, we aimed at introducing the role of kinetoplast DNA (kDNA) and dependent topoisomerases (TPI) as potential chemotherapeutic targets for treatment of leishmaniasis. The Leishmania parasite has a mitochondrial DNA located in the attached circles. KDNA replication process is very complex and a large number of proteins are involved. Some of them are classified as topoisomerases, which play major biological roles in the effective cell processes in the topology, synthesis, and organization of kDNA and constitute the main drug target in kinetoplast for leishmaniasis cure. Several studies have shown that the inhibitors of TPI exchange these enzymes into intracellular cell toxins and provide an appropriate tool for killing the parasite in the host. DNA binding drugs have also been reported as therapeutic agents against leishmanial infections.

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