ReviewJournal of neuroscience research2026
The Endoterpenoid System: A Membrane-Based Logic Framework for Integrating Cannabinoid, Olfactory, and Lipid-Sensitive Receptor Crosstalk.
Review in Journal of neuroscience research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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Authors and funding
5 authors.
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Abstract
The Endoterpenoid System (ETS) is a proposed new membrane-based framework that ensembles classical endocannabinoid signaling (ECS) with ectopically expressed olfactory GPCRs, ion channels, and microbially derived terpenoids. Integrated with this model is the proposed endoterpenoidome (eTBome) machine: a chemically diverse pool of endogenous cannabinoids, dietary terpenoids, and microbial metabolites whose lipophilicity drives partitioning into cholesterol-rich lipid rafts. Within these nanoscale microdomains, ETS components undergo co-localization and co-expression, enabling receptor heteromerization and β-arrestin-scaffolded signalosomes that facilitate dynamic crosstalk and emergent responses such as bistable apoptotic switches and context specific modulation of Gᵢ/o, Gₛ/olf, and Gq pathways. We detail molecular mechanisms underpinning ETS behavior, including lipid mediated allostery, scaffold protein recruitment, and lateral diffusion effects, and highlight the gut microbiota as pivotal architects of the eTBome through terpene synthase-driven production of bioactive ligands. Germ free and antibiotic treated animal models underscore the dependence of ETS ligand pools and receptor distributions on microbial colonization. This article proposes key avenues for experimental validation, including high resolution structural studies of CB-OR heteromers, quantitative lipidomic mapping of eTBome distributions, live cell super resolution imaging of receptor nanoclusters, and gnotobiotic manipulations of microbial terpene synthesis. By introducing them as proposals to the scientific community and by integrating ECS/eCBome biology with olfactory receptor (OR) and microbial metabolite research, the ETS/eTBome concept offers a cohesive hypothesis for lipid-driven GPCR crosstalk and indicated non-standard targets for therapeutic modulation in cancer, neuroinflammation, and metabolic disorders.
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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 Socratic graph.