{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:23:58Z","timestamp":1789154638259,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["386893015"],"award-info":[{"award-number":["386893015"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005224","name":"German Center for Neurodegenerative Diseases","doi-asserted-by":"publisher","award":["VH-NG-1021"],"award-info":[{"award-number":["VH-NG-1021"]}],"id":[{"id":"10.13039\/501100005224","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Columbia University Medical Center","award":["Schaefer Research Scholars Awards"],"award-info":[{"award-number":["Schaefer Research Scholars Awards"]}]},{"name":"National Institute of Health","award":["R56AG069118"],"award-info":[{"award-number":["R56AG069118"]}]},{"name":"National Institute of Health","award":["R56AG066889"],"award-info":[{"award-number":["R56AG066889"]}]},{"name":"National Institute of Health","award":["R56AG051876"],"award-info":[{"award-number":["R56AG051876"]}]},{"name":"National Institute of Health","award":["R01AG067501"],"award-info":[{"award-number":["R01AG067501"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neurogenesis decreases in Alzheimer\u2019s disease (AD) patients, suggesting that restoring the normal neurogenic response could be a disease modifying intervention. To study the mechanisms of pathology-induced neuro-regeneration in vertebrate brains, zebrafish is an excellent model due to its extensive neural regeneration capacity. Here, we report that Kynurenic acid (KYNA), a metabolite of the amino acid tryptophan, negatively regulates neural stem cell (NSC) plasticity in adult zebrafish brain through its receptor, aryl hydrocarbon receptor 2 (Ahr2). The production of KYNA is suppressed after amyloid-toxicity through reduction of the levels of Kynurenine amino transferase 2 (KAT2), the key enzyme producing KYNA. NSC proliferation is enhanced by an antagonist for Ahr2 and is reduced with Ahr2 agonists or KYNA. A subset of Ahr2-expressing zebrafish NSCs do not express other regulatory receptors such as il4r or ngfra, indicating that ahr2-positive NSCs constitute a new subset of neural progenitors that are responsive to amyloid-toxicity. By performing transcriptome-wide association studies (TWAS) in three late onset Alzheimer disease (LOAD) brain autopsy cohorts, we also found that several genes that are components of KYNA metabolism or AHR signaling are differentially expressed in LOAD, suggesting a strong link between KYNA\/Ahr2 signaling axis to neurogenesis in LOAD.<\/jats:p>","DOI":"10.3390\/cells10102748","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T09:10:49Z","timestamp":1634202649000},"page":"2748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["KYNA\/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0625-9710","authenticated-orcid":false,"given":"Tohid","family":"Siddiqui","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) within Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabesh","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) within Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislava","family":"Popova","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) within Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-3902","authenticated-orcid":false,"given":"Mehmet Ilyas","family":"Cosacak","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) within Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Sariya","sequence":"additional","affiliation":[{"name":"The Department of Neurology, The Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"B-CUBE, Center for Molecular Bioengineering, TU Dresden, Tatzberg 41, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mayeux","sequence":"additional","affiliation":[{"name":"The Department of Neurology, The Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tosto","sequence":"additional","affiliation":[{"name":"The Department of Neurology, The Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-9762","authenticated-orcid":false,"given":"Caghan","family":"Kizil","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) within Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany"},{"name":"The Department of Neurology, The Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The Cellular Phase of Alzheimer\u2019s Disease","volume":"164","author":"Karran","year":"2016","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/nature02264","article-title":"Folding proteins in fatal ways","volume":"426","author":"Selkoe","year":"2003","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.1074069","article-title":"Alzheimer\u2019s disease is a synaptic 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