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Targeting CNS Related Protist Pathogens: Calcium Ion Dependency in the Brain-Eating Amoebae

Abdul Mannan Baig1, Areeba Khaleeq1, Fizza Nazim1

  • 1Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan.

ACS Chemical Neuroscience
|December 17, 2019
PubMed

Insights

Free-living amoebae (FLA), or brain-eating amoebae, cause deadly encephalitis. Targeting their calcium ion dependency with existing drugs shows promise for new treatments.

Area of Science:

  • Neuroparasitology
  • Molecular Biology
  • Drug Discovery

Background:

  • Free-living amoebae (FLA) like *Naegleria fowleri*, *Balamuthia mandrillaris*, and *Acanthamoeba* spp. cause severe encephalitis with high mortality.
  • Current treatments are limited due to diagnostic delays, lack of novel drug development, and incomplete understanding of FLA biology.
  • The study hypothesizes that calcium ion (Ca2+) dependency is a critical vulnerability in FLA pathogenicity.

Discussion:

  • Genomic, transcriptomic, and proteomic data were analyzed to identify Ca2+ influx channels in FLA.
  • The research focused on targeting human-like voltage-gated Ca2+ channels.
  • Existing non-infectious disease drugs, nifedipine and verapamil, were tested against *Acanthamoeba* spp. trophozoites.

Key Insights:

  • FLA possess various Ca2+ ion influx regulating channels, suggesting a reliance on calcium.
  • Human-like voltage-gated Ca2+ channels present a potential therapeutic target.
  • Nifedipine and verapamil demonstrated effects on *Acanthamoeba* spp. trophozoites, indicating potential repurposing.

Outlook:

  • Further investigation into Ca2+ channel function and drug efficacy is warranted.
  • This research opens avenues for developing novel therapeutics against brain-eating amoebae.
  • Repurposing existing drugs could accelerate treatment development for amoebic encephalitis.
Keywords:
Acanthamoeba keratitisAcanthamoeba, neurolepticsbioinformatics computational toolsparasitic brain diseasepromethazinerepurposing of drugs

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