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Lactate transport and receptor actions in cerebral malaria

Shelton T Mariga1, Miriam Kolko2, Albert Gjedde1

  • 1Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.

Frontiers in Neuroscience
|June 7, 2014
PubMed

Insights

Cerebral malaria (CM) may stem from brain energy metabolism issues. Malaria parasites disrupt brain lactate balance, suggesting monocarboxylate transporters (MCTs) and GPR81 as potential therapeutic targets for CM.

Area of Science:

  • Neurology
  • Infectious Diseases
  • Biochemistry

Background:

  • Cerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection, predominantly affecting children in tropical regions.
  • High mortality rates and intractable seizures characterize CM, with current treatments proving insufficient.
  • Understanding the underlying pathogenesis of CM is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the role of cerebral energy metabolic defects in the pathogenesis of cerebral malaria.
  • To explore monocarboxylate transporters (MCTs) and the lactate receptor GPR81 as potential therapeutic targets in CM.

Main Methods:

  • Review of existing literature on malaria parasite metabolism and brain energy homeostasis.
  • Analysis of the role of lactate production by malaria parasites.
  • Examination of the function of monocarboxylate transporters (MCTs) in lactate transport.
  • Investigation of the recently discovered lactate receptor GPR81.

Main Results:

  • Malaria parasites significantly consume glucose, leading to increased lactate production.
  • Monocarboxylate transporters (MCTs) facilitate lactate transfer, influencing brain metabolic signaling.
  • High parasite-derived lactate may compromise the blood-brain barrier and disrupt brain lactate homeostasis.
  • Lactate binding to GPR81 on brain cells and vasculature inhibits adenylyl cyclase.

Conclusions:

  • Cerebral energy metabolic defects, particularly related to lactate, are implicated in CM pathogenesis.
  • Monocarboxylate transporters (MCTs) and the lactate receptor GPR81 represent promising novel therapeutic targets for managing cerebral malaria.

Keywords:
cerebral malariaenergy metabolismlactate receptorlactate transportvolume transmitter

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