{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T09:14:10Z","timestamp":1793351650592,"version":"4.5.0"},"reference-count":216,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a transcription factor that regulates the expression of different genes involved in essential biological processes, including cell proliferation, neuronal development, immune response, cellular stress, apoptosis, DNA repair, and angiogenesis. The gene encoding this transcription factor is called NR4A2 and has been identified as an immediate early gene. Moreover, research in animal models and clinical trials has suggested an association between reduced NR4A2 gene expression and some neurodegenerative diseases and psychiatric disorders. These include Parkinson\u2019s disease, Alzheimer\u2019s disease progression, schizophrenia, substance abuse (alcohol and amphetamines), neurodevelopmental disorders, and cognitive imairment. NR4A2 activity is controlled at multiple levels, including transcriptional and post-transcriptional regulation of its gene expression, such as translational and post-translational processes. This review summarizes the current knowledge of the NR4A2 gene, encompassing its structure and the molecular mechanisms that regulate its expression. The key epigenetic mechanisms that regulate its gene expression are emphasized, including DNA methylation, histone deacetylation, and regulation by microRNAs. It also addresses its role in central nervous system pathologies associated with dysregulation of NR4A2 gene expression. Finally, we discuss the potential of these regulatory mechanisms as biomarkers and therapeutic targets for neurodegenerative diseases and psychiatric disorders.<\/jats:p>","DOI":"10.3390\/ijms26189162","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T12:33:32Z","timestamp":1758285212000},"page":"9162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Regulation of NR4A2 Gene Expression and Its Importance in Neurodegenerative and Psychiatric Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-0532","authenticated-orcid":false,"given":"Elizabeth","family":"Ruiz-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Laboratorio de Neuroqu\u00edmica, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Su\u00e1rez S.S., Avenida Insurgentes Sur. No. 3877, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Rojas","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Circuito Escolar s\/n, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Yescas G\u00f3mez","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Su\u00e1rez S.S., Avenida Insurgentes Sur. No. 3877, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-983X","authenticated-orcid":false,"given":"Nancy","family":"Mart\u00ednez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Epidemiologica en Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Dr M\u00e1rquez 162, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel Alberto","family":"Ruiz-Chow","sequence":"additional","affiliation":[{"name":"Unidad de Neuropsiquiatr\u00eda, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Su\u00e1rez S.S., Avenida Insurgentes Sur. No. 3877, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Nava-Ruiz","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuropatolog\u00eda Experimental, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Su\u00e1rez S.S., Avenida Insurgentes Sur. No. 3877, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7969-0942","authenticated-orcid":false,"given":"Gabriela","family":"Ib\u00e1\u00f1\u00e9z-Cervantes","sequence":"additional","affiliation":[{"name":"Departamento de Desarrollo de Tecnolog\u00edas, Centro Interdisciplinario de Ciencias Marinas (CICIMAR-IPN), Instituto Polit\u00e9cnico Nacional, C. 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