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The Gaseous Neurotransmitter Nitric Oxide: A Potential Therapeutic Target for Neuropsychiatric and Neurodegenerative Disorders

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Applied Chemistry".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 4536

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Special Issue Editor

Prof. Dr. Nikolaos Pitsikas

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Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larisa, Greece
Interests: behavioral pharmacology; neuroscience; psychopharmacology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The search of novel molecules in therapy is a hot issue. The gaseous neurotransmitter nitric oxide is intensively studied for its implication in a wide range of neuropsychiatric and neurodegenerative diseases, including anxiety, depression, schizophrenia, dementia, Parkinson disease, Alzheimer’s disease, etc.

This Special Issue of Molecules aims to assess new advances of the therapeutic action of nitric oxide and its modulators targeting different pathologies. In this context, we intend to highlight and emphasize their pharmacological activity.

We cordially invite researchers working in the field to contribute original research articles, as well as critical review articles, that unravel the therapeutic potential of nitric oxide and its modulators.

We look forward to receiving your contributions.

Prof. Dr. Nikolaos Pitsikas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

nitric oxide
biological targets
pharmacology
neuropsychiatric disorders
neurodegenerative disorders

Published Papers (4 papers)

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Research

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20 pages, 3277 KiB

Open AccessArticle

The Impact of LY487379 or CDPPB on eNOS Expression in the Mouse Brain and the Effect of Joint Administration of Compounds with NO^• Releasers on MK-801- or Scopolamine-Driven Cognitive Dysfunction in Mice

by Agata Płoska, Anna Siekierzycka, Paulina Cieślik, Lawrence W. Dobrucki, Leszek Kalinowski and Joanna M. Wierońska

Molecules 2024, 29(3), 627; https://doi.org/10.3390/molecules29030627 - 29 Jan 2024

Viewed by 771

Abstract

The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain pathologies, including schizophrenia or Alzheimer’s disease (AD). Positive allosteric modulators (PAMs) of metabotropic glutamate (mGlu) receptors were shown to be effective procognitive compounds, but little is known about their impact on eNOS expression and stability. Here, we investigated the influence of the acute and chronic administration of LY487379 or CDPPB (mGlu2 and mGlu5 PAMs), on eNOS expression in the mouse brain and the effect of the joint administration of the ligands with nitric oxide (NO) releasers, spermineNONOate or DETANONOate, in different combinations of doses, on MK-801- or scopolamine-induced amnesia in the novel object recognition (NOR) test. Our results indicate that both compounds provoked eNOS monomer formation, and CDPPB at a dose of 5 mg/kg exaggerated the effect of MK-801 or scopolamine. The coadministration of spermineNONOate or DETANONOate enhanced the antiamnesic effect of CDPPB or LY487379. The best activity was observed for ineffective or moderate dose combinations. The results indicate that treatment with mGluR2 and mGluR5 PAMs may be burdened with the risk of promoting eNOS uncoupling through the induction of dimer dissociation. Administration of the lowest possible doses of the compounds with NO^• donors, which themselves have procognitive efficacy, may be proposed for the treatment of schizophrenia or AD. Full article

(This article belongs to the Special Issue The Gaseous Neurotransmitter Nitric Oxide: A Potential Therapeutic Target for Neuropsychiatric and Neurodegenerative Disorders)

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15 pages, 1968 KiB

Open AccessArticle

The Nitric Oxide (NO) Donor Molsidomine Attenuates Memory Impairments Induced by the D1/D2 Dopaminergic Receptor Agonist Apomorphine in the Rat

by Foteini Vartzoka, Elif Ozenoglu and Nikolaos Pitsikas

Molecules 2023, 28(19), 6861; https://doi.org/10.3390/molecules28196861 - 28 Sep 2023

Cited by 2 | Viewed by 793

Abstract

Several lines of evidence suggest that scarcity of the gaseous molecule nitric oxide (NO) is associated with the pathogenesis of schizophrenia. Therefore, compounds, such as NO donors, that can normalize NO levels might be of utility for the treatment of this pathology. It has been previously shown that the NO donor molsidomine attenuated schizophrenia-like behavioral deficits caused by glutamate hypofunction in rats. The aim of the current study was to investigate the efficacy of molsidomine and that of the joint administration of this NO donor with sub-effective doses of the non-typical antipsychotics clozapine and risperidone to counteract memory deficits associated with dysregulation of the brain dopaminergic system in rats. Molsidomine (2 and 4 mg/kg) attenuated spatial recognition and emotional memory deficits induced by the mixed dopamine (DA) D₁/D₂ receptor agonist apomorphine (0.5 mg/kg). Further, the joint administration of sub-effective doses of molsidomine (1 mg/kg) with those of clozapine (0.1 mg/kg) or risperidone (0.03 mg/kg) counteracted non-spatial recognition memory impairments caused by apomorphine. The present findings propose that molsidomine is sensitive to DA dysregulation since it attenuates memory deficits induced by apomorphine. Further, the current findings reinforce the potential of molsidomine as a complementary molecule for the treatment of schizophrenia. Full article

(This article belongs to the Special Issue The Gaseous Neurotransmitter Nitric Oxide: A Potential Therapeutic Target for Neuropsychiatric and Neurodegenerative Disorders)

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Review

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35 pages, 2532 KiB

Open AccessReview

“NO” Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD

by Mariana G. Fronza, Bruna F. Ferreira, Isabela Pavan-Silva, Francisco S. Guimarães and Sabrina F. Lisboa

Molecules 2024, 29(1), 89; https://doi.org/10.3390/molecules29010089 - 22 Dec 2023

Viewed by 1146

Abstract

Post-traumatic 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. Full article

(This article belongs to the Special Issue The Gaseous Neurotransmitter Nitric Oxide: A Potential Therapeutic Target for Neuropsychiatric and Neurodegenerative Disorders)

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Graphical abstract

14 pages, 2949 KiB

Open AccessReview

Neuronal Nitric Oxide Synthase and Post-Translational Modifications in the Development of Central Nervous System Diseases: Implications and Regulation

by Cristina Maccallini and Rosa Amoroso

Molecules 2023, 28(18), 6691; https://doi.org/10.3390/molecules28186691 - 19 Sep 2023

Cited by 1 | Viewed by 1485

Abstract

In the Central Nervous System (CNS), Nitric Oxide (NO) is mainly biosynthesized by neuronal Nitric Oxide Synthase (nNOS). The dysregulated activation of nNOS in neurons is critical in the development of different conditions affecting the CNS. The excessive production of NO by nNOS is responsible for a number of proteins’ post-translational modifications (PTMs), which can lead to aberrant biochemical pathways, impairing CNS functions. In this review, we briefly revise the main implications of dysregulated nNOS in the progression of the most prevalent CNS neurodegenerative disorders, i.e., Alzheimer’s disease (AD) and Parkinson’s disease, as well as in the development of neuronal disorders. Moreover, a specific focus on compounds able to modulate nNOS activity as promising therapeutics to tackle different neuronal diseases is presented. Full article

(This article belongs to the Special Issue The Gaseous Neurotransmitter Nitric Oxide: A Potential Therapeutic Target for Neuropsychiatric and Neurodegenerative Disorders)

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