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stress disorder (PTSD) is a psychiatric condition characterized by persistent fear responses and altered neurotransmitter functioning due to traumatic experiences. Stress predominantly affects glutamate, a neurotransmitter crucial for synaptic plasticity and memory formation. Activation of the N-Methyl-D-Aspartate glutamate receptors (NMDAR) can trigger the formation of a complex comprising postsynaptic density protein-95 (PSD95), the neuronal nitric oxide synthase (nNOS), and its adaptor protein (NOS1AP). This complex is pivotal in activating nNOS and nitric oxide (NO) production, which, in turn, activates downstream pathways that modulate neuronal signaling, including synaptic plasticity\/transmission, inflammation, and cell death. The involvement of nNOS and NOS1AP in the susceptibility of PTSD and its comorbidities has been widely shown. Therefore, understanding the interplay between stress, fear, and NO is essential for comprehending the maintenance and progression of PTSD, since NO is involved in fear acquisition and extinction processes. Moreover, NO induces post-translational modifications (PTMs), including S-nitrosylation and nitration, which alter protein function and structure for intracellular signaling. Although evidence suggests that NO influences synaptic plasticity and memory processing, the specific role of PTMs in the pathophysiology of PTSD remains unclear. This review highlights pathways modulated by NO that could be relevant to stress and PTSD.<\/jats:p>","DOI":"10.3390\/molecules29010089","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T08:53:01Z","timestamp":1703235181000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["\u201cNO\u201d Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD"],"prefix":"10.3390","volume":"29","author":[{"given":"Mariana G.","family":"Fronza","sequence":"first","affiliation":[{"name":"Pharmacology Departament, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna F.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Pharmacology Departament, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela","family":"Pavan-Silva","sequence":"additional","affiliation":[{"name":"Pharmacology Departament, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco S.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Pharmacology Departament, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2069-3524","authenticated-orcid":false,"given":"Sabrina F.","family":"Lisboa","sequence":"additional","affiliation":[{"name":"Pharmacology Departament, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 14049-900, Brazil"},{"name":"Biomolecular Sciences Department, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, S\u00e3o Paulo 14040-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nrendo.2009.106","article-title":"Stress and disorders of the stress system","volume":"5","author":"Chrousos","year":"2009","journal-title":"Nat. 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