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Genetic and Molecular Regulations of Neuronal Activity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 15962

Special Issue Editors


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Guest Editor
Department of Medical, Oral and Biotechnological Sciences, Unit of Immunodiagnostic and Molecular Pathology, University “G.d’Annunzio”, Via Dei Vestini 31, 66100 Chieti, Italy
Interests: neuroimmunology; inflammation; cytokines; non-neuronal cholinergic system; peripheral biomarkers of neurodegeneration; inflammation/autoimmunity
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Guest Editor
NIH National Institute on Aging (NIA), Translat Gerontol Branch, Baltimore, MD 21225, USA
Interests: Alzheimer's and Parkinson's disease; traumatic brain injury; ischemic stroke

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Guest Editor
Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy
Interests: neuroscience; medicine biochemistry; genetics and molecular biology pharmacology

Special Issue Information

Dear Colleagues, 

I am delighted to announce a new Special Issue of the International Journal of Molecular Sciences, entitled “Genetic and Molecular Regulations of Neuronal Activity”, devoted to recent research that focuses on the association between genes or proteins and neuronal activity in neurodegenerative disorders.

This aim of this Special Issue is to provide an overview of the current status and new achievements in drug therapy for neurodegenerative diseases. Reviews are particularly welcome.

The advances in molecular biology and gene regulation knowledge have driven innovations in neuroscience. The regulation of the transcription of many genes—but also the splicing, trafficking and translation of mRNA—are involved in controlling protein levels and their ultimate localization and role. Within neurons, multiple gene regulatory mechanisms are essential to the healthy development and function of the nervous system. Genetic mutations and the regulation of gene expression may play a critical role in abberant neuronal development and occurrence of neurological disorders.

The topics include but are not limited to:

  • mRNA splicing, microRNAs, epigenetic modifications and controling translation in the developing and mature nervous system;
  • The molecular mechanisms underlying neuronal dysfunction;
  • Neuronal dysfuncion and neurodegenerative diseases;
  • The translation of neuronal dysfunction therapeutics from bench to bedside.

Prof. Dr. Marcella Reale
Dr. Nigel H. Greig
Prof. Dr. Cesar Borlongan
Prof. Dr. Anna Rosa Carta
Guest Editors

Manuscript Submission Information

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Keywords

  • neurodegeneration
  • neurological disorder
  • neurotherapeutics
  • gene regulation
  • neurogenetics
  • neuroinflammation

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Published Papers (6 papers)

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Editorial

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4 pages, 192 KiB  
Editorial
Genetic and Molecular Regulations of Neuronal Activity
by Marcella Reale, Cesar Borlongan, Anna R. Carta and Nigel H. Greig
Int. J. Mol. Sci. 2023, 24(22), 16191; https://doi.org/10.3390/ijms242216191 - 10 Nov 2023
Viewed by 846
Abstract
This Special Issue of the International Journal of Molecular Sciences (IJMS) focuses on ‘Genetic and Molecular Regulations of Neuronal Activity’ [...] Full article
(This article belongs to the Special Issue Genetic and Molecular Regulations of Neuronal Activity)

Research

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12 pages, 3485 KiB  
Article
Lactoferrin Modulates Induction of Transcription Factor c-Fos in Neuronal Cultures
by Marina Yu. Kopaeva, Asya M. Azieva, Anton B. Cherepov and Irina Yu. Zarayskaya
Int. J. Mol. Sci. 2023, 24(9), 8373; https://doi.org/10.3390/ijms24098373 - 6 May 2023
Cited by 3 | Viewed by 1815
Abstract
Lactoferrin (Lf) is a multifunctional protein from the transferrin family. Of particular interest is the ability of Lf to affect a wide range of neuronal processes by modulating the expression of genes involved in long-term neuroplasticity. The expression of the immediate early gene [...] Read more.
Lactoferrin (Lf) is a multifunctional protein from the transferrin family. Of particular interest is the ability of Lf to affect a wide range of neuronal processes by modulating the expression of genes involved in long-term neuroplasticity. The expression of the immediate early gene c-fos that is rapidly activated in response to external influences, and its product, transcription factor c-Fos, is widely used as a marker of long-term neuronal plasticity. The present study aims to examine the effect of human Lf on the induction of transcription factor c-Fos in the primary mouse neuronal cultures after stimulation and to determine the cellular localization of human Lf and its colocalization with induced c-Fos protein. Primary dissociated cultures of hippocampal cells were obtained from the brains of newborn C57BL/6 mice (P0-P1). On day 7 of culturing, human Lf was added to the medium. After 24 h (day 8 in culture), c-Fos protein was induced in cells by triple application of 50 mM KCl. c-Fos content was analyzed using the immunofluorescent method 2 h after stimulation. Stimulation promoted exogenous Lf translocation into the nuclei of cultured neuronal cells, which correlated with increased induction of transcription factor c-Fos and was accompanied by nuclear colocalization of these proteins. These results attest to the potential of Lf as a modulator of neuronal processes and open up new prospects in studying the mechanisms of the regulatory effects of lactoferrin on cell function. Full article
(This article belongs to the Special Issue Genetic and Molecular Regulations of Neuronal Activity)
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18 pages, 2322 KiB  
Article
Ribosomal RACK1 Regulates the Dendritic Arborization by Repressing FMRP Activity
by Nicla Romano, Bruna Di Giacomo, Veronica Nobile, Antonella Borreca, Daniela Willems, Francesca Tilesi, Elisabetta Catalani, Manasi Agrawal, Kristy Welshhans, Sara Ricciardi, Davide Cervia and Marcello Ceci
Int. J. Mol. Sci. 2022, 23(19), 11857; https://doi.org/10.3390/ijms231911857 - 6 Oct 2022
Cited by 10 | Viewed by 2931
Abstract
FMRP is an RNA-binding protein that represses the translation of specific mRNAs. In neurons, its depletion determines the exaggerated translation of mRNAs leading to dendritic and axonal aberrant development, two peculiar features of Fragile X syndrome patients. However, how FMRP binds to translational [...] Read more.
FMRP is an RNA-binding protein that represses the translation of specific mRNAs. In neurons, its depletion determines the exaggerated translation of mRNAs leading to dendritic and axonal aberrant development, two peculiar features of Fragile X syndrome patients. However, how FMRP binds to translational machinery to regulate the translation of its mRNA targets is not yet fully understood. Here, we show that FMRP localizes on translational machinery by interacting with the ribosomal binding protein, Receptor for Activated C Kinase 1 (RACK1). The binding of FMRP to RACK1 removes the translational repressive activity of FMRP and promotes the translation of PSD-95 mRNA, one specific target of FMRP. This binding also results in a reduction in the level of FMRP phosphorylation. We also find that the morphological abnormalities induced by Fmr1 siRNA in cortical neurons are rescued by the overexpression of a mutant form of RACK1 that cannot bind ribosomes. Thus, these results provide a new mechanism underlying FMRP activity that contributes to altered development in FXS. Moreover, these data confirm the role of ribosomal RACK1 as a ribosomal scaffold for RNA binding proteins. Full article
(This article belongs to the Special Issue Genetic and Molecular Regulations of Neuronal Activity)
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Review

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32 pages, 2376 KiB  
Review
Deciphering the Tubulin Language: Molecular Determinants and Readout Mechanisms of the Tubulin Code in Neurons
by Riccardo Zocchi, Claudia Compagnucci, Enrico Bertini and Antonella Sferra
Int. J. Mol. Sci. 2023, 24(3), 2781; https://doi.org/10.3390/ijms24032781 - 1 Feb 2023
Cited by 3 | Viewed by 3125
Abstract
Microtubules (MTs) are dynamic components of the cell cytoskeleton involved in several cellular functions, such as structural support, migration and intracellular trafficking. Despite their high similarity, MTs have functional heterogeneity that is generated by the incorporation into the MT lattice of different tubulin [...] Read more.
Microtubules (MTs) are dynamic components of the cell cytoskeleton involved in several cellular functions, such as structural support, migration and intracellular trafficking. Despite their high similarity, MTs have functional heterogeneity that is generated by the incorporation into the MT lattice of different tubulin gene products and by their post-translational modifications (PTMs). Such regulations, besides modulating the tubulin composition of MTs, create on their surface a “biochemical code” that is translated, through the action of protein effectors, into specific MT-based functions. This code, known as “tubulin code”, plays an important role in neuronal cells, whose highly specialized morphologies and activities depend on the correct functioning of the MT cytoskeleton and on its interplay with a myriad of MT-interacting proteins. In recent years, a growing number of mutations in genes encoding for tubulins, MT-interacting proteins and enzymes that post-translationally modify MTs, which are the main players of the tubulin code, have been linked to neurodegenerative processes or abnormalities in neural migration, differentiation and connectivity. Nevertheless, the exact molecular mechanisms through which the cell writes and, downstream, MT-interacting proteins decipher the tubulin code are still largely uncharted. The purpose of this review is to describe the molecular determinants and the readout mechanisms of the tubulin code, and briefly elucidate how they coordinate MT behavior during critical neuronal events, such as neuron migration, maturation and axonal transport. Full article
(This article belongs to the Special Issue Genetic and Molecular Regulations of Neuronal Activity)
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20 pages, 331 KiB  
Review
Novel Approaches in Molecular Imaging and Neuroimaging of Fibromyalgia
by Maria Ricci, Andrea Cimini, Maria Rosaria Grivet Fojaja, Mariacristina Ullo, Bruno Carabellese, Viviana Frantellizzi and Ennio Lubrano
Int. J. Mol. Sci. 2022, 23(24), 15519; https://doi.org/10.3390/ijms232415519 - 8 Dec 2022
Cited by 8 | Viewed by 2578
Abstract
Fibromyalgia (FM) represents a condition that is still controversial in its entity, pathophysiology, diagnosis and management. The aim of this review is to focus on imaging aspects of FM, especially on novel approaches in molecular imaging, with a special focus on neuroimaging. Novel [...] Read more.
Fibromyalgia (FM) represents a condition that is still controversial in its entity, pathophysiology, diagnosis and management. The aim of this review is to focus on imaging aspects of FM, especially on novel approaches in molecular imaging, with a special focus on neuroimaging. Novel functional and molecular imaging findings may represent, eventually, future biomarkers both in research settings and in terms of clinical practice. Several imaging techniques have already been tested in clinical trials in the FM field, including functional MRI, positron emission tomography (PET) imaging with 18F-FDG in FM, PET imaging of the dopaminergic system, PET imaging of the GABAergic system, PET imaging with neuroinflammation and neuroimmune parameters, PET imaging of the opioid system and H215O-PET activation studies. Therefore, the potential role in the FM field of fMRI and different PET tracers has been discussed in different settings, serving as a comprehensive guide of novel imaging options both in research and in the clinical field. Full article
(This article belongs to the Special Issue Genetic and Molecular Regulations of Neuronal Activity)
14 pages, 1071 KiB  
Review
Role of Vitronectin and Its Receptors in Neuronal Function and Neurodegenerative Diseases
by Yelizhati Ruzha, Junjun Ni, Zhenzhen Quan, Hui Li and Hong Qing
Int. J. Mol. Sci. 2022, 23(20), 12387; https://doi.org/10.3390/ijms232012387 - 16 Oct 2022
Cited by 12 | Viewed by 3487
Abstract
Vitronectin (VTN), a multifunctional glycoprotein with various physiological functions, exists in plasma and the extracellular matrix. It is known to be involved in the cell attachment, spreading and migration through binding to the integrin receptor, mainly via the RGD sequence. VTN is also [...] Read more.
Vitronectin (VTN), a multifunctional glycoprotein with various physiological functions, exists in plasma and the extracellular matrix. It is known to be involved in the cell attachment, spreading and migration through binding to the integrin receptor, mainly via the RGD sequence. VTN is also widely used in the maintenance and expansion of pluripotent stem cells, but its effects go beyond that. Recent evidence shows more functions of VTN in the nervous system as it participates in neural differentiation, neuronutrition and neurogenesis, as well as in regulating axon size, supporting and guiding neurite extension. Furthermore, VTN was proved to play a key role in protecting the brain as it can reduce the permeability of the blood–brain barrier by interacting with integrin receptors in vascular endothelial cells. Moreover, evidence suggests that VTN is associated with neurodegenerative diseases, such as Alzheimer’s disease, but its function has not been fully understood. This review summarizes the functions of VTN and its receptors in neurons and describes the role of VTN in the blood–brain barrier and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Genetic and Molecular Regulations of Neuronal Activity)
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