The emerging paradigm of calcium homeostasis as a new therapeutic target for protozoan parasites

Yash Gupta, Steven Goicoechea, Catherine M. Pearce, Raman Mathur, Jesus G. Romero, Samuel K. Kwofie, Matthew C. Weyenberg, Bharathi Daravath, Neha Sharma, Poonam, Hoseah M. Akala, Stefan M. Kanzok, Ravi Durvasula, Brijesh Rathi, Prakasha Kempaiah

Research output: Contribution to journalReview articlepeer-review

Abstract

Calcium channels (CCs), a group of ubiquitously expressed membrane proteins, are involved in many pathophysiological processes of protozoan parasites. Our understanding of CCs in cell signaling, organelle function, cellular homeostasis, and cell cycle control has led to improved insights into their structure and functions. In this article, we discuss CCs characteristics of five major protozoan parasites Plasmodium, Leishmania, Toxoplasma, Trypanosoma, and Cryptosporidium. We provide a comprehensive review of current antiparasitic drugs and the potential of using CCs as new therapeutic targets. Interestingly, previous studies have demonstrated that human CC modulators can kill or sensitize parasites to antiparasitic drugs. Still, none of the parasite CCs, pumps, or transporters has been validated as drug targets. Information for this review draws from extensive data mining of genome sequences, chemical library screenings, and drug design studies. Parasitic resistance to currently approved therapeutics is a serious and emerging threat to both disease control and management efforts. In this article, we suggest that the disruption of calcium homeostasis may be an effective approach to develop new anti-parasite drug candidates and reduce parasite resistance.

Original languageEnglish (US)
Pages (from-to)56-82
Number of pages27
JournalMedicinal Research Reviews
Volume42
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • apicomplexa
  • calcium channel modulators
  • calcium homeostasis
  • cryptosporidium
  • drug resistance
  • kinetoplastida
  • Leishmania
  • Plasmodium
  • protozoan parasites
  • SERCA and non-SERCA pump inhibitors
  • target-based drug discovery
  • Toxoplasma
  • Trypanosoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Fingerprint

Dive into the research topics of 'The emerging paradigm of calcium homeostasis as a new therapeutic target for protozoan parasites'. Together they form a unique fingerprint.

Cite this