Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024530 (
malaria
)
44,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The replication cycle and pathogenesis of the Plasmodium malarial parasite involves rapid expansion in red blood cells (RBCs), and variants of certain RBC-specific proteins protect against
malaria
in humans. In RBCs,
bisphosphoglycerate mutase
(
BPGM
) acts as a key allosteric regulator of hemoglobin/oxyhemoglobin. We demonstrate here that a loss-of-function mutation in the murine Bpgm (Bpgm
L166P
) gene confers protection against both Plasmodium-induced cerebral
malaria
and blood-stage
malaria
. The
malaria
protection seen in Bpgm
L166P
mutant mice is associated with reduced blood parasitemia levels, milder clinical symptoms, and increased survival. The protective effect of Bpgm
L166P
involves a dual mechanism that enhances the host's stress erythroid response to Plasmodium-driven RBC loss and simultaneously alters the intracellular milieu of the RBCs, including increased oxyhemoglobin and reduced energy metabolism, reducing Plasmodium maturation, and replication. Overall, our study highlights the importance of
BPGM
as a regulator of hemoglobin/oxyhemoglobin in
malaria
pathogenesis and suggests a new potential
malaria
therapeutic target.
...
PMID:Bisphosphoglycerate Mutase Deficiency Protects against Cerebral Malaria and Severe Malaria-Induced Anemia. 3296 87
