Table of contents
Cutaneous Leishmaniasis is a debilitating disease caused by intracellular parasites, presenting a challenge due to the lack of a decisive and safe treatment for Zoonotic Cutaneous Leishmaniasis (ZCL) (Hadighi et al. 2006). However, in a groundbreaking study, researchers have adopted a new approach to tackle this problem. Inhibition of apoptosis, a mechanism employed by intracellular pathogens to ensure long-term survival within their host cells, has been identified as a key factor in this context (Laskay et al. 2003). This article explores the significance of miRNAs (microRNAs) in the context of Leishmaniasis treatment, shedding light on their potential to revolutionize therapeutic approaches against these parasites (Manzano-Román and Siles-Lucas 2012).
Research and Discussion
The Role of miRNAs in Parasite Biology
MicroRNAs, known for their significant impact on various biological processes, have emerged as potential candidates in the fight against Leishmaniasis (Manzano-Román and Siles-Lucas 2012). These small non-coding RNAs are responsible for regulating developmental and physiological processes in parasites (Liu et al. 2010). Therefore, the identification and characterization of miRNAs in Leishmania could be instrumental in discovering new drug targets against the disease (Sahoo et al. 2014).
The Pathogenesis of Leishmaniasis
When Leishmania promastigotes are injected into the skin, they are swiftly phagocytized by Polymorphonuclear Neutrophils (PMNs) and macrophages, transforming into amastigotes (Frank et al. 2015). Infected cells are known to neutralize invasive pathogens by initiating apoptosis, a form of programmed cell death. However, Leishmania infection inhibits apoptosis in macrophages, allowing the parasites to evade host defense mechanisms (Moore and Matlashewsk 1994).
MicroRNA-Mediated Apoptosis in Leishmania
Recent studies have demonstrated that specific miRNAs play a crucial role in apoptosis regulation in Leishmania. For instance, miR-15a has been found to target anti-apoptotic genes like BCL-2, leading to the cleavage of caspase 9 and caspase 3/7 (Abdullah et al. 2019; Zhang et al. 2011). Additionally, miR-155 targets Caspase-3 mRNA in activated macrophages, influencing apoptosis in RAW 264.7 cell line (De Santis et al. 2016).
Exploring miRNA Therapy for Leishmaniasis
In this study, researchers utilized miRNA therapy to assess whether miR-15a mimic and/or miR-155 inhibitor could induce apoptosis in L.major-infected cells and reduce parasite burden. The results showed that miR-155 inhibition and miR-15a mimic treatments increased apoptosis in normal and infected macrophages in RAW 264.7 cell line. While miR-15a mimic or miR-155 inhibitor alone did not increase the expression of caspase 3, they did significantly decrease the parasite load in the spleen of BALB/c mice.
Comparison with Previous Studies
Earlier research by Resende et al. demonstrated that miR-15a down-regulated expression and up-regulated B-cell lymphoma-2 (Bcl-2) mRNA in Odontogenic Keratocyst (OKC) samples (Resende et al. 2018). Our study corroborated these findings, as miR-15a mimic and miR-155 inhibitor treatments did not increase caspase 3 expression but did reduce the parasite load. Similarly, targeting anti-apoptotic miR-21 has shown promise in treating pancreatic cancer in mice (Sicard et al. 2013).
Findings and Future Directions
The study's findings suggest that miR-155 inhibition and miR-15a mimic have the potential to induce apoptosis in Leishmania-infected cells, offering a promising therapeutic protocol for treating Leishmaniasis. However, further investigations on the safety and side effects of miRNA therapy in L.major-infected mice are necessary to address any concerns related to conventional drug toxicity.
The lack of an effective and safe treatment for Zoonotic Cutaneous Leishmaniasis (ZCL) has been a significant challenge. However, a new approach focusing on miRNA therapy has shown promising results in inducing apoptosis and reducing parasite load. By inhibiting miR-155 and mimicking miR-15a, researchers have paved the way for potential breakthroughs in the treatment of Leishmaniasis. Continued research and development in this area hold the promise of providing a decisive solution for this debilitating disease, benefiting millions of affected individuals worldwide.
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