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Neuroglobin from Brain Protection to Cancer Progression
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Neuroglobin from Brain Protection to Cancer Progression

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 14171

Special Issue Editors

Dr. Roberta Misasi

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Guest Editor
Dept. of Experimental Medicine, Università degli Studi di Roma La Sapienza, Rome, Italy
Prof. Dr. Maria Marino

E-Mail Website
Guest Editor
Dipartimento di Scienze, Università Roma Tre, Rome, Italy
Interests: endocrine disrupters; phthalate; alkylphenols; BPA; organohalogenates; environmental monitoring; biological monitoring; reprotoxicity; thyroid; metabolic effects
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Margherita Ruoppolo

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
Interests: inherited metabolic disorders; metabolomics; newborn screening; proteomics; protein-protein interaction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neuroglobin (Ngb) is a globin that is physiologically expressed in a widespread manner and in modest quantities in the brain areas and in the peripheral nervous system. Its cerebral distribution and its active role as an oxidative stress sensor and cytoprotective factor against redox imbalance lead us to consider that Ngb is part of endogenous neuroprotective pathways and elucidating a new scenario in the possibility of discovering new therapeutic approaches. In fact, the increase in Ngb levels protects neurons from oxidative stress, glutamate toxicity and apoptosis, with a clear protective effect against neurodegeneration.

However, Ngb has recently been recognized as a new tumor-associated protein, highlighting the role of this globin in regulating both the stress-induced apoptotic pathway and the antioxidant systems activated by cancer cells. Although the exact role of Ngb as a cancer promoter or tumor suppressor is still debated, some evidence of increased Ngb expression in nervous system tumors, related to the degree of malignancy, suggests a critical role for Ngb in neoplastic growth.

In recent years, efforts have been made to investigate the molecular mechanisms underlying the neuroprotective effects of Ngb, which, however, when they occur in tumors, may confer to Ngb a critical role in tumor progression.

Dr. Roberta Misasi
Prof. Maria Marino
Prof. Margherita Ruoppolo
Guest Editors

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. Cells 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

  • oxidative stress and antioxidant systems
  • reactive oxygen species (ROS)
  • mitochondrial dysfunction
  • neuroprotection and neurodegenerative diseases
  • apoptosis
  • autophagy
  • tumor progression in the nervous system
  • proteic signature
  • onteratomics

Published Papers (6 papers)

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Editorial

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3 pages, 197 KiB  
Editorial
Editorial for Special Issue: Neuroglobin from Brain Protection to Cancer Progression
by Maria Marino, Roberta Misasi and Margherita Ruoppolo
Cells 2022, 11(14), 2181; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11142181 - 13 Jul 2022
Viewed by 1001
Abstract
Since its discovery in 2000 [...] Full article
(This article belongs to the Special Issue Neuroglobin from Brain Protection to Cancer Progression)

Research

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18 pages, 3007 KiB  
Article
Overexpression of Neuroglobin Promotes Energy Metabolism and Autophagy Induction in Human Neuroblastoma SH-SY5Y Cells
by Valeria Manganelli, Illari Salvatori, Michele Costanzo, Antonella Capozzi, Daniela Caissutti, Marianna Caterino, Cristiana Valle, Alberto Ferri, Maurizio Sorice, Margherita Ruoppolo, Tina Garofalo and Roberta Misasi
Cells 2021, 10(12), 3394; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10123394 - 02 Dec 2021
Cited by 14 | Viewed by 2885
Abstract
Neuroglobin (NGB) is an O2-binding globin mainly expressed in the central and peripheral nervous systems and cerebrospinal fluid. Previously, it was demonstrated that NGB overexpression protects cells from hypoxia-induced death. To investigate processes promoted by NGB overexpression, we used a cellular [...] Read more.
Neuroglobin (NGB) is an O2-binding globin mainly expressed in the central and peripheral nervous systems and cerebrospinal fluid. Previously, it was demonstrated that NGB overexpression protects cells from hypoxia-induced death. To investigate processes promoted by NGB overexpression, we used a cellular model of neuroblastoma stably overexpressing an NGB-FLAG construct. We used a proteomic approach to identify the specific profile following NGB overexpression. To evaluate the role of NGB overexpression in increasing energetic metabolism, we measured oxygen consumption rate (OCR) and the extracellular acidification rate through Seahorse XF technology. The effect on autophagy induction was evaluated by analyzing SQSTM1/p62 and LC3-II expression. Proteomic analysis revealed several differentially regulated proteins, involved in oxidative phosphorylation and integral mitochondrial proteins linked to energy metabolism. The analysis of mitochondrial metabolism demonstrated that NGB overexpression increases mitochondrial ATP production. Indeed, NGB overexpression enhances bioenergetic metabolism, increasing OCR and oxygen consumption. Analysis of autophagy induction revealed an increase of LC3-II together with a significant decrease of SQSTM1/p62, and NGB-LC3-II association during autophagosome formation. These results highlight the active participation of NGB in several cellular processes that can be upregulated in response to NGB overexpression, playing a role in the adaptive response to stress in neuroblastoma cells. Full article
(This article belongs to the Special Issue Neuroglobin from Brain Protection to Cancer Progression)
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13 pages, 1859 KiB  
Article
Neuroglobin: A New Possible Marker of Estrogen-Responsive Breast Cancer
by Virginia Solar Fernandez, Marco Fiocchetti, Manuela Cipolletti, Marco Segatto, Paolo Cercola, Annalisa Massari, Sabrina Ghinassi, Francesco Cavaliere and Maria Marino
Cells 2021, 10(8), 1986; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10081986 - 05 Aug 2021
Cited by 3 | Viewed by 2226
Abstract
The expression of the α-subtype of Estrogen Receptor (ERα) characterizes most breast cancers (more than 75%), for which endocrine therapy is the mainstay for their treatment. However, a high percentage of ERα+ breast cancers are de novo or acquired resistance to endocrine therapy, [...] Read more.
The expression of the α-subtype of Estrogen Receptor (ERα) characterizes most breast cancers (more than 75%), for which endocrine therapy is the mainstay for their treatment. However, a high percentage of ERα+ breast cancers are de novo or acquired resistance to endocrine therapy, and the definition of new targets for improving therapeutic interventions and the prediction of treatment response is demanding. Our previous data identified the ERα/AKT/neuroglobin (NGB) pathway as a common pro-survival process activated in different ERα breast cancer cell lines. However, no in vivo association between the globin and the malignity of breast cancer has yet been done. Here, we evaluated the levels and localization of NGB in ERα+ breast ductal carcinoma tissue of different grades derived from pre-and post-menopausal patients. The results indicate a strong association between NGB accumulation, ERα, AKT activation, and the G3 grade, while no association with the menopausal state has been evidenced. Analyses of the data set (e.g., GOBO) strengthen the idea that NGB accumulation could be linked to tumor cell aggressiveness (high grade) and resistance to treatment. These data support the view that NGB accumulation, mainly related to ER expression and tumor grade, represents a compensatory process, which allows cancer cells to survive in an unfavorable environment. Full article
(This article belongs to the Special Issue Neuroglobin from Brain Protection to Cancer Progression)
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Review

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19 pages, 2201 KiB  
Review
Structural and (Pseudo-)Enzymatic Properties of Neuroglobin: Its Possible Role in Neuroprotection
by Giovanna De Simone, Diego Sbardella, Francesco Oddone, Alessandra Pesce, Massimo Coletta and Paolo Ascenzi
Cells 2021, 10(12), 3366; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10123366 - 30 Nov 2021
Cited by 9 | Viewed by 2152
Abstract
Neuroglobin (Ngb), the third member of the globin family, was discovered in human and murine brains in 2000. This monomeric globin is structurally similar to myoglobin (Mb) and hemoglobin (Hb) α and β subunits, but it hosts a bis-histidyl six-coordinated heme-Fe atom. Therefore, [...] Read more.
Neuroglobin (Ngb), the third member of the globin family, was discovered in human and murine brains in 2000. This monomeric globin is structurally similar to myoglobin (Mb) and hemoglobin (Hb) α and β subunits, but it hosts a bis-histidyl six-coordinated heme-Fe atom. Therefore, the heme-based reactivity of Ngb is modulated by the dissociation of the distal HisE7-heme-Fe bond, which reflects in turn the redox state of the cell. The high Ngb levels (~100–200 μM) present in the retinal ganglion cell layer and in the optic nerve facilitate the O2 buffer and delivery. In contrast, the very low levels of Ngb (~1 μM) in most tissues and organs support (pseudo-)enzymatic properties including NO/O2 metabolism, peroxynitrite and free radical scavenging, nitrite, hydroxylamine, hydrogen sulfide reduction, and the nitration of aromatic compounds. Here, structural and (pseudo-)enzymatic properties of Ngb, which are at the root of tissue and organ protection, are reviewed, envisaging a possible role in the protection from neuronal degeneration of the retina and the optic nerve. Full article
(This article belongs to the Special Issue Neuroglobin from Brain Protection to Cancer Progression)
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14 pages, 1253 KiB  
Review
Neuroglobin in Retinal Neurodegeneration: A Potential Target in Therapeutic Approaches
by Virginia Solar Fernandez, Maria Marino and Marco Fiocchetti
Cells 2021, 10(11), 3200; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10113200 - 17 Nov 2021
Cited by 5 | Viewed by 2038
Abstract
Retinal neurodegeneration affects an increasing number of people worldwide causing vision impairments and blindness, reducing quality of life, and generating a great economic challenge. Due to the complexity of the tissue, and the diversity of retinal neurodegenerative diseases in terms of etiology and [...] Read more.
Retinal neurodegeneration affects an increasing number of people worldwide causing vision impairments and blindness, reducing quality of life, and generating a great economic challenge. Due to the complexity of the tissue, and the diversity of retinal neurodegenerative diseases in terms of etiology and clinical presentation, so far, there are no cures and only a few early pathological markers have been identified. Increasing efforts have been made to identify and potentiate endogenous protective mechanisms or to abolish detrimental stress responses to preserve retinal structure and function. The discovering of the intracellular monomeric globin neuroglobin (NGB), found at high concentration in the retina, has opened new possibilities for the treatment of retinal disease. Indeed, the NGB capability to reversibly bind oxygen and its neuroprotective function against several types of insults including oxidative stress, ischemia, and neurodegenerative conditions have raised the interest in the possible role of the globin as oxygen supplier in the retina and as a target for retinal neurodegeneration. Here, we provide the undercurrent knowledge on NGB distribution in retinal layers and the evidence about the connection between NGB level modulation and the functional outcome in terms of retinal neuroprotection to provide a novel therapeutic/preventive target for visual pathway degenerative disease. Full article
(This article belongs to the Special Issue Neuroglobin from Brain Protection to Cancer Progression)
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12 pages, 722 KiB  
Review
Role of Neuroglobin in the Neuroprotective Actions of Estradiol and Estrogenic Compounds
by George E. Barreto, Andrew J. McGovern and Luis M. Garcia-Segura
Cells 2021, 10(8), 1907; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10081907 - 27 Jul 2021
Cited by 14 | Viewed by 3001
Abstract
Estradiol exerts neuroprotective actions that are mediated by the regulation of a variety of signaling pathways and homeostatic molecules. Among these is neuroglobin, which is upregulated by estradiol and translocated to the mitochondria to sustain neuronal and glial cell adaptation to injury. In [...] Read more.
Estradiol exerts neuroprotective actions that are mediated by the regulation of a variety of signaling pathways and homeostatic molecules. Among these is neuroglobin, which is upregulated by estradiol and translocated to the mitochondria to sustain neuronal and glial cell adaptation to injury. In this paper, we will discuss the role of neuroglobin in the neuroprotective mechanisms elicited by estradiol acting on neurons, astrocytes and microglia. We will also consider the role of neuroglobin in the neuroprotective actions of clinically relevant synthetic steroids, such as tibolone. Finally, the possible contribution of the estrogenic regulation of neuroglobin to the generation of sex differences in brain pathology and the potential application of neuroglobin as therapy against neurological diseases will be examined. Full article
(This article belongs to the Special Issue Neuroglobin from Brain Protection to Cancer Progression)
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