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TSPO in the Pathways of Neuroinflammation and Apoptosis
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TSPO in the Pathways of Neuroinflammation and Apoptosis

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Neuroscience".

Deadline for manuscript submissions: closed (1 April 2021) | Viewed by 4392

Special Issue Editors

Dr. Sheelu Monga

E-Mail Website
Guest Editor
Ruth and Bruce Rappaport Faculty of Medicine, Technion- Israel Institute of Technology, Haifa 31096, Israel
Interests: neuroinflammation and apoptosis
Prof. Moshe Gavish

E-Mail Website
Guest Editor
Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Sara & Moshe Zisapel Nanoelectronics Center, Technion City, Haifa 32000, Israel
Interests: drug development for treatment of brain diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

The 18 kDa translocator protein (TSPO) is known to possess immunomodulatory effects. In addition, TSPO plays a role in other biological functions, such as steroidogenesis, apoptosis, differentiation of neuronal progenitor cells, cholesterol transport, mitochondrial respiration, mitochondrial permeability transition pore opening, and cellular proliferation.

Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites, or autoimmunity. In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues. The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood–brain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells.

TSPO ligands can affect inflammatory processes. The primary intracellular location of TSPO is the outer mitochondrial membrane. Interestingly, TSPO and its ligands also appear to be involved in microglia activation, which may have therapeutic implications. In addition, TSPO expression is upregulated in different pathological conditions such as brain ischemia, certain forms of epilepsy, glioma, and inflammatory peripheral neuropathy.

In this Special Issue, we consider the impact of neuroinflammation, apoptosis/necrosis, and ROS generation on TSPO expression. We seek to explore the different pathways of inflammation, how this inflammation leads to cell death, and the factors which are responsible for it.

Dr. Sheelu Monga
Prof. Moshe Gavish
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. Biology is an international peer-reviewed open access monthly 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

  • TSPO 
  • inflammation 
  • microglia 
  • macrophages 
  • apoptosis
  • cytokines 
  • chemokines 
  • M1 and M2 inflammatory pathway

Published Papers (2 papers)

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Research

10 pages, 2940 KiB  
Article
The Neuro-Protective Effects of the TSPO Ligands CB86 and CB204 on 6-OHDA-Induced PC12 Cell Death as an In Vitro Model for Parkinson’s Disease
by Sheelu Monga, Nunzio Denora, Valentino Laquintana, Rami Yashaev, Abraham Weizman and Moshe Gavish
Biology 2021, 10(11), 1183; https://doi.org/10.3390/biology10111183 - 15 Nov 2021
Viewed by 1945
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder which is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Oxidative stress or reactive oxygen species (ROS) generation was suggested to play a role in this specific type of neurodegeneration. Therapeutic options [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder which is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Oxidative stress or reactive oxygen species (ROS) generation was suggested to play a role in this specific type of neurodegeneration. Therapeutic options which can target and counteract ROS generation may be of benefit. TSPO ligands are known to counteract with neuro-inflammation, ROS generation, apoptosis, and necrosis. In the current study, we investigated an in vitro cellular PD model by the assessment of 6-hydroxydopamine (6-OHDA, 80 µM)-induced PC12 neurotoxicity. Simultaneously to the exposure of the cells to 6-OHDA, we added the TSPO ligands CB86 and CB204 (25 µM each) and assessed the impact on several markers of cell death. The two ligands normalized significantly (57% and 52% respectively, from 44%; whereas the control was 68%) cell proliferation at different time points from 0–24 h. Additionally, we evaluated the effect of these two TSPO ligands on necrosis using propidium iodide (PI) staining and found that the ligands inhibited significantly the 6-OHDA-induced necrosis. As compared to control, the red count was increased up to 57-fold whereas CB86 and CB204 inhibited to 2.7-fold and 3.2-fold respectively. Necrosis was also analyzed by LDH assay which showed significant effect. Both assays demonstrated similar potent anti-necrotic effect of the two TSPO ligands. Reactive oxygen species (ROS) generation induced by 6-OHDA was also inhibited by the two TSPO ligand up to 1.3 and 1.5-fold respectively, as compared to 6-OHDA group. CB86 and CB204 inhibited also normalized the cell viability up to 1.8-fold after the exposure to 6-OHDA, as assessed by XTT assay. The two TSPO ligands also inhibited apoptosis significantly (1.3-fold for both) as assessed by apopxin green staining. In summary, it appears that the two TSPO ligands CB86 and CB204 can suppress cell death of PC12 induced by 6-OHDA. The results may be relevant to the use of these two TSPO ligands as therapeutic option neurodegenerative diseases like PD. Full article
(This article belongs to the Special Issue TSPO in the Pathways of Neuroinflammation and Apoptosis)
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21 pages, 8031 KiB  
Article
The TSPO Ligands MGV-1 and 2-Cl-MGV-1 Differentially Inhibit the Cigarette Smoke-Induced Cytotoxicity to H1299 Lung Cancer Cells
by Nidal Zeineh, Rafael M. Nagler, Martin Gabay, Fadi Obeid, Meygal Kahana, Abraham Weizman and Moshe Gavish
Biology 2021, 10(5), 395; https://doi.org/10.3390/biology10050395 - 2 May 2021
Cited by 2 | Viewed by 1948
Abstract
TSPO is involved in cigarette smoke (CS)-induced cellular toxicity, which may result in oral and pulmonary diseases and lung cancer. H1299 lung cancer cells were exposed directly to CS. The H1299 cells were pretreated with our TSPO ligands MGV-1 and 2-Cl-MGV-1 (Ki = [...] Read more.
TSPO is involved in cigarette smoke (CS)-induced cellular toxicity, which may result in oral and pulmonary diseases and lung cancer. H1299 lung cancer cells were exposed directly to CS. The H1299 cells were pretreated with our TSPO ligands MGV-1 and 2-Cl-MGV-1 (Ki = 825 nM for both) at a concentration of 25 µM 24 h prior to CS exposure. Cell death and apoptotic markers were measured, in addition to TSPO expression levels, ATP synthase activity, generation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (ΔΨm), cAMP and LDH levels. Pretreatment with MGV-1 and 2-Cl-MGV-1 (25 µM), 24 h prior to CS exposure, differentially attenuated the CS-induced cellular insult as well as cell death in H1299 lung cancer cells. These protective effects included prevention of ATP synthase reversal, ROS generation, depolarization of the mitochondrial membrane and elevation in LDH. The preventive efficacy of 2-Cl-MGV-1 was superior to that achieved by MGV-1. Both ligands did not prevent the elevation in cAMP. These findings may indicate a mild protective effect of these TSPO ligands in CS-related pulmonary and keratinocyte cellular pathology. Full article
(This article belongs to the Special Issue TSPO in the Pathways of Neuroinflammation and Apoptosis)
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