Programmed cell death pathways as targets for developing antifilarial drugs: Lessons from the recent findings

More than half a century has passed since the introduction of the National Filariasis Control Program; however, as of 2023, lymphatic filariasis (LF) still prevails globally, particularly in the tropical and subtropical regions, posing a substantial challenge to the objective of worldwide elimination. LF is affecting human beings and its economically important livestock leading to a crucial contributor to morbidities and disabilities. The current scenario has been blowing up alarms of attention to develop potent therapeutics and strategies having efficiency against the adult stage of filarial nematodes. In this context, the exploration of a suitable drug target that ensures lethality to macro and microfilariae is now our first goal to achieve. Apoptosis has been the potential target across all three stages of filarial nematodes viz. oocytes, microfilariae (mf) and adults resulting in filarial death after receiving the signal from the reactive oxygen species (ROS) and executed through intrinsic and extrinsic pathways. Hence, it is considered a leading target for developing antifilarial drugs. Herein, we have shown the efficacy of several natural and synthetic compounds/nanoformulations in triggering the apoptotic death of filarial parasites with little or no toxicity to the host body system.

Automated summary

More than 50 years have passed since the start of the National Filariasis Control Program, but lymphatic filariasis (LF) remains prevalent globally, especially in tropical and subtropical regions, posing a major challenge to global elimination efforts. LF affects humans and economically important livestock, contributing significantly to morbidity and disabilities. Developing effective therapeutics and strategies against the adult stage of filarial nematodes has become crucial. Apoptosis has emerged as a promising target for developing antifilarial drugs, as it induces filarial death through reactive oxygen species (ROS) signals and intrinsic and extrinsic pathways. Various natural and synthetic compounds/nanoformulations have shown efficacy in triggering apoptotic death in filarial parasites with minimal toxicity to the host body.