ReviewCell communication and signaling : CCS2026
The mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.
Review in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interplay between metabolic pathways and immune responses is critical for understanding host-parasite interactions in protozoan infections. This review examines the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways-key routes for isoprenoid synthesis essential for sterol production and bioactive compounds. Beyond sustaining parasite survival, these pathways directly influence host immune signaling cascades, including NF-κB, MAPK, PI3K/Akt, and mTOR. A critical conceptual distinction is introduced: genuine "moonlighting" functions-where a single enzyme performs two distinct molecular roles-are currently documented only for mevalonate kinase in trypanosomatids. Leishmania donovani secretes mevalonate kinase (LdMVK), which has been associated with modulation of macrophage inflammatory signaling and attenuation of NF-κB-dependent cytokine responses. Similarly, Trypanosoma cruzi mevalonate kinase (TcMVK) alters host calcium signaling and MAPK activation, promoting parasite invasion. By contrast, most effects described in the literature-such as trained immunity induction or Th1/Th2 skewing following statin treatment-represent pleiotropic consequences of canonical pathway disruption. Therapeutically, the absence of the MEP pathway in humans and structural divergence of parasitic MVA enzymes enable selective targeting. Strategies include drug repurposing (statins, bisphosphonates), novel enzyme inhibitors, and immunomodulatory approaches. However, parasitic metabolic plasticity and host toxicity remain challenges, supporting "double-hit" combination therapies that simultaneously disrupt parasite metabolism and block salvage pathways to overcome resistance. By integrating metabolic essentiality with immune signaling, MVA/MEP pathways emerge as multifunctional hubs offering promising avenues for precision therapies and vaccines against neglected tropical diseases.
Indexed as
Identifiers
42888444What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.