Targeting Host Glycolysis as a Strategy for Antimalarial Development.
Plasmodium
antimalarial
enolase
erythrocyte
glycolysis
malaria
oxidative stress
red blood cells
Journal
Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359
Informations de publication
Date de publication:
2021
2021
Historique:
received:
24
06
2021
accepted:
17
08
2021
entrez:
4
10
2021
pubmed:
5
10
2021
medline:
21
10
2021
Statut:
epublish
Résumé
Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase - a critical enzyme in glycolysis - and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather than direct hemolysis. We apply our model of red cell toxicity to address questions regarding erythrocyte glycolytic disruption in the context of
Identifiants
pubmed: 34604112
doi: 10.3389/fcimb.2021.730413
pmc: PMC8482815
doi:
Substances chimiques
Antimalarials
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
730413Subventions
Organisme : NIAID NIH HHS
ID : R01 AI103280
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI130584
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007511
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026891
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI123808
Pays : United States
Informations de copyright
Copyright © 2021 Jezewski, Lin, Reisz, Culp-Hill, Barekatain, Yan, D’Alessandro, Muller and Odom John.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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