ReviewFrontiers in neuroscience2026
Ligand-specific duality of aryl hydrocarbon receptor signaling in cognitive health: from environmental neurotoxicity to microbiome-mediated neuroprotection.
Review in Frontiers in neuroscience, 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
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aromatic hydrocarbon receptor (AhR) is a key molecular interface integrating environmental chemical signals with host-microbiome metabolism, with profound effects on brain function. This review systematically addresses the ligand-specific duality of AhR signaling in cognitive health, comparing the predominantly neurotoxic signaling driven by environmental polycyclic aromatic hydrocarbons (PAHs) with the predominantly neuroprotective signaling mediated by gut microbiota-derived tryptophan metabolites. However, this dichotomy is context-dependent rather than absolute. PAHs activate AhR in a sustained, high-affinity manner, engaging downstream NF-κB neuroinflammation, NLRP3 inflammasome activation, oxidative stress, synaptic dysfunction, and transgenerational epigenetic alterations. In contrast, microbiota-derived metabolites such as indole-3-propionic acid (IPA) and kynurenic acid (KYNA) elicit transient, low-affinity AhR activation that engages cell-type-specific programs promoting anti-inflammatory responses, neurogenesis, blood-brain barrier integrity, and neuronal homeostasis. Critically, the outcome of AhR activation is modulated by ligand pharmacokinetics, cell-type identity, temporal dynamics of receptor engagement, and tissue-specific co-factor availability. These contextual variables determine whether AhR functions as a driver of neurodegeneration or a guardian of cognitive resilience. We further examine the divergent roles of AhR in Alzheimer's and Parkinson's diseases, where the balance between detrimental and protective ligands determines disease progression. Finally, we discuss therapeutic strategies targeting the AhR-gut-brain axis, including dietary modulation, probiotic interventions, and selective AhR modulators. Understanding the context-dependent outcomes of AhR activation provides a framework for developing precision approaches to preserve cognitive function and prevent neurodegeneration.
Indexed as
Identifiers
What 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.