{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:19:50Z","timestamp":1793387990075,"version":"4.5.0"},"reference-count":125,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia, mainly affecting elderly individuals. AD is characterized by \u03b2-amyloid plaques, abnormal tau tangles, neuronal loss, and metabolic disruptions. Recent studies have revealed the involvement of the kynurenine (KP) pathway and the aryl hydrocarbon receptor (AhR) in AD development. The KP pathway metabolizes tryptophan to produce neuroactive substances like kynurenine, kynurenic acid, and quinolinic acid. In AD, high levels of kynurenine and the neurotoxic quinolinic acid are associated with increased neuroinflammation and excitotoxicity; conversely, reduced levels of kynurenic acid, which acts as a glutamate receptor antagonist, compromise neuroprotection. Research has indicated elevated KP metabolites and enzymes in the hippocampus of AD patients and other tissues such as blood, cerebrospinal fluid, and urine. However, the finding that KP metabolites are AD biomarkers in blood, cerebrospinal fluid, and urine has been controversial. This controversy, stemming from the lack of consideration of the specific stage of AD, details of the patient\u2019s treatment, cognitive deficits, and psychiatric comorbidities, underscores the need for more comprehensive research. AhR, a ligand-activated transcription factor, regulates immune response, oxidative stress, and xenobiotic metabolism. Various ligands, including tryptophan metabolites, can activate it. Some studies suggest that AhR activation contributes to AD, while others propose that it provides neuroprotection. This discrepancy may be explained by the specific ligands that activate AhR, highlighting the complex relationship between the KP pathway, AhR activation, and AD, where the same pathway can produce both neuroprotective and harmful effects.<\/jats:p>","DOI":"10.3390\/brainsci14090950","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T09:46:20Z","timestamp":1727343980000},"page":"950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The Kynurenine Pathway, Aryl Hydrocarbon Receptor, and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6240-3468","authenticated-orcid":false,"given":"Enoc Mariano","family":"Cort\u00e9s Malag\u00f3n","sequence":"first","affiliation":[{"name":"Research Division, Hospital Ju\u00e1rez de M\u00e9xico, Mexico City 07760, Mexico"},{"name":"Genetics Laboratory, Hospital Nacional Homeop\u00e1tico, Mexico City 06800, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"L\u00f3pez Ornelas","sequence":"additional","affiliation":[{"name":"Research Division, Hospital Ju\u00e1rez de M\u00e9xico, Mexico City 07760, Mexico"},{"name":"Genetics Laboratory, Hospital Nacional Homeop\u00e1tico, Mexico City 06800, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irlanda","family":"Olvera G\u00f3mez","sequence":"additional","affiliation":[{"name":"Research Division, Hospital Ju\u00e1rez de M\u00e9xico, Mexico City 07760, Mexico"},{"name":"Facultad Ciencias de la Salud, Universidad An\u00e1huac Norte, Estado de M\u00e9xico 52786, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9690-1940","authenticated-orcid":false,"given":"Jos\u00e9","family":"Bonilla Delgado","sequence":"additional","affiliation":[{"name":"Research Unit, Hospital Regional de Alta Especialidad de Ixtapaluca, IMSS-BINESTAR, Ixtapaluca 56530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1212\/WNL.54.11.2072","article-title":"Age-specific incidence rates of Alzheimer\u2019s disease: The Baltimore Longitudinal Study of Aging","volume":"54","author":"Kawas","year":"2000","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, X., Feng, X., Sun, X., Hou, N., Han, F., and Liu, Y. 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