{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:01:08Z","timestamp":1792803668915,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Krembil Foundation","id":[{"id":"https:\/\/ror.org\/037svw098","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Weston Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The need to identify new potentially druggable biochemical mechanisms for Alzheimer\u2019s disease (AD) is an ongoing priority. The therapeutic limitations of amyloid-based approaches are further motivating this search. Amino acid metabolism, particularly tryptophan metabolism, has the potential to emerge as a leading candidate and an alternative exploitable biomolecular target. Multiple avenues support this contention. Tryptophan (trp) and its associated metabolites are able to inhibit various enzymes participating in the biosynthesis of \u03b2-amyloid, and one metabolite, 3-hydroxyanthranilate, is able to directly inhibit neurotoxic \u03b2-amyloid oligomerization; however, whilst certain trp metabolites are neuroprotectant, other metabolites, such as quinolinic acid, are directly toxic to neurons and may themselves contribute to AD progression. Trp metabolites also have the ability to influence microglia and associated cytokines in order to modulate the neuroinflammatory and neuroimmune factors which trigger pro-inflammatory cytotoxicity in AD. Finally, trp and various metabolites, including melatonin, are regulators of sleep, with disorders of sleep being an important risk factor for the development of AD. Thus, the involvement of trp biochemistry in AD is multifactorial and offers a plethora of druggable targets in the continuing quest for AD therapeutics.<\/jats:p>","DOI":"10.3390\/brainsci13020292","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T01:59:43Z","timestamp":1675907983000},"page":"292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["The Role of Tryptophan Metabolism in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Karl","family":"Savonije","sequence":"first","affiliation":[{"name":"Krembil Research Institute, Toronto Western Hospital, 60 Leonard Avenue, Rm 4KD477, Toronto, ON M5T 0S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald F.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Krembil Research Institute, Toronto Western Hospital, 60 Leonard Avenue, Rm 4KD477, Toronto, ON M5T 0S8, Canada"},{"name":"Departments of Medicine (Neurology) and Chemistry, University of Toronto, Toronto, ON M5T 0S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1017\/cjn.2016.36","article-title":"The Prevalence and Incidence of Dementia Due to Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis","volume":"43","author":"Fiest","year":"2016","journal-title":"Can. 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