Authors
Laura Bertarini, Federico Imbeni, Virginia Brighenti, Isabella Martusciello, Federica Pellati, Silvia Alboni
Published in
ACS pharmacology & translational science. Volume 8. Issue 10. Pages 3432-3452. Oct 10, 2025. Epub Sep 15, 2025.
Abstract
p-Cresol (pC) is a phenolic compound to which humans can be exposed through both environmental sources, such as a pollutant, and endogenous production by the gut microbiota. Among microbial contributors, Clostridioides difficile appears to be a major source of pC within the body. Once absorbed, pC is highly protein-bound in plasma and predominantly circulates in its hepatic conjugated forms: p-cresyl sulfate (pCS) and p-cresol glucuronide (pCG), which are mainly excreted in urine. Accumulation of these metabolites, particularly pCS, classified as a protein-bound uremic toxin, has been associated with the progression of chronic kidney disease (CKD) and related complications, due to its pro-oxidant, pro-inflammatory, and pro-apoptotic properties. CKD patients are at increased risk for cognitive impairment, affective disorders, and central nervous system (CNS) dysfunctions. In recent years, increasing evidence has suggested a potential role of pC and its metabolites in CNS diseases. Here, we summarize current knowledge on the involvement of these compounds in the pathogenesis and progression of autism spectrum disorder, Parkinson's disease, Alzheimer's disease, and post-traumatic stress disorder. We also discuss how modulating systemic levels of pC may represent a promising strategy to improve pathological phenotypes in the context of neurodevelopmental and neurodegenerative disorders.
PMID:
41098572
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.
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