{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T04:40:12Z","timestamp":1759034412343,"version":"3.44.0"},"reference-count":50,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CONACYT","award":["FOSISS-290526"],"award-info":[{"award-number":["FOSISS-290526"]}]},{"name":"SECIHTI","award":["CBF-2023-2024-457"],"award-info":[{"award-number":["CBF-2023-2024-457"]}]},{"name":"Spanish AEI","award":["AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["AEI\/10.13039\/501100011033"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Smell dysfunction affects quality of life and is considered an early clinical sign of Alzheimer\u2019s and Parkinson\u2019s diseases. Olfactory loss increases with age and is associated with certain ciliopathies, a group of genetic disorders characterized by a wide spectrum of multisystemic disturbances. The dysfunction of mature olfactory sensory neurons (OSNs) in the olfactory neuronal pathway remains poorly understood. Previous evidence suggests that primary cilia proteins are involved in the maturation of olfactory sensory neurons (OSNs). In this study, we obtained olfactory neuronal precursors (ONPs) from the olfactory mucosa of young and older healthy volunteers who reported smell impairment (hyposmia) without neurological deficits or underlying airflow issues (conductive olfactory loss) and from normosmic individuals. In vitro analysis of ONPs showed that these cells can form primary cilia in normosmic individuals, while in hyposmic participants, there is a reduction in cilia frequency and a shorter length. In addition, ONPs from hyposmic individuals had a decrease in proliferation and cell differentiation. Our data indicate that alterations in molecular pathways related to primary cilia formation and the proliferation of ONPs lead to defects in neuronal maturation. These changes may hinder the differentiation of olfactory sensory neurons OSNs and contribute, at least in part, to olfactory loss.<\/jats:p>","DOI":"10.3390\/ijms26199435","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T14:50:38Z","timestamp":1758898238000},"page":"9435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impaired Formation of Primary Cilia in Olfactory Neuronal Precursors Is Associated with Decreased Proliferation and Maturation in Individuals with Hyposmia"],"prefix":"10.3390","volume":"26","author":[{"given":"Salvador","family":"Alarc\u00f3n-Elizalde","sequence":"first","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Lora-Castellanos","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Santill\u00e1n-Morales","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6589-7902","authenticated-orcid":false,"given":"Miguel A.","family":"Res\u00e9ndiz-Gach\u00fas","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Estrada-Reyes","sequence":"additional","affiliation":[{"name":"Laboratorio de Fitofarmacolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juli\u00e1n","family":"Oikawa-Sala","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6995-2996","authenticated-orcid":false,"given":"Jes\u00fas","family":"Mu\u00f1oz-Estrada","sequence":"additional","affiliation":[{"name":"Department of Computational Biomedicine, Cedars Sinai Medical Center, Los Angeles, CA 90069, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4346-1547","authenticated-orcid":false,"given":"Lilian","family":"Mayagoitia-Novales","sequence":"additional","affiliation":[{"name":"Departamento de Etolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A.","family":"Constantino-Jonapa","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1139-4642","authenticated-orcid":false,"given":"Cristina","family":"Mart\u00edn-Higueras","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Institute of Biomedical Technologies (ITB), University of La Laguna (ULL), 38200 Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0020-1913","authenticated-orcid":false,"given":"\u00c1ngel","family":"Acebes","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Institute of Biomedical Technologies (ITB), University of La Laguna (ULL), 38200 Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Ben\u00edtez-King","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.anorl.2010.09.007","article-title":"Olfactory System and Emotion: Common Substrates","volume":"128","author":"Soudry","year":"2011","journal-title":"Eur. 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