Krebs cycle enzymes for targeted therapeutics and immunotherapy for anti-leishmanial drug development using: Pathways, potential targets, and future perspectives

Abstract

Leishmaniasis is a parasitic and neglected tropical disease which majorly impacts poor and developing nations. One of the significant factors that impacts the severity of the pathological condition includes the socioeconomic background of the affected region. The rise of drug-resistant Leishmania is a serious concern for the effectiveness of the present treatment. As a result, the drug options need to be relooked immediately. Leishmania employs Krebs cycle intermediates for its needs after infection for establishing various defense mechanisms to escape the host immune responses. Nevertheless, a variety of immunological reactions are also seen during infection, which clear the parasites. One of the more promising strategies in this regard would involve combining targeted therapy and immunotherapy. The targeted treatments work by obstructing vital pathways that are required for Leishmania to grow and survive. The mechanism of action of immunotherapy is the control of the host immune response, which entails the blockage of molecular pathways essential for the growth and maintenance of the parasite. The Krebs cycle intermediates have important biochemical roles. Additionally, in macrophages and dendritic cells, they play roles as signalling molecules for controlling inflammatory responses. The review brings together the available literature about the importance of Krebs cycle metabolites as potential treatment targets for leishmaniasis. © 2022 Elsevier Inc.