Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
Advances in translocator protein (TSPO) research
share announcement

Advances in translocator protein (TSPO) research

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 8046

Special Issue Editor

Dr. Leo Veenman

E-Mail Website
Guest Editor
Consorzio per Valutazioni Biologiche e Farmacologiche, Via Nicolò Putignani, 178, 70122 Bari, Italy
Interests: drug development; brain disease and injury; mitochondrial function; genomics/non-genomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The 18 kDa translocator protein (TSPO) is a receptor molecule expressed throughout the body, including in the brain. At the cellular level, the primary location of this 18 kDa protein is the outer mitochondrial membrane (OMM). TSPO was originally discovered as a secondary binding site for the benzodiazepine, diazepam. However, TSPO shows no homology whatsoever with the central benzodiazepine receptor (CBR) and is encoded by its own gene, the TSPO gene.  TSPO is known to be involved in numerous functions, for example, cholesterol transport over the outer mitochondrial membrane, steroidogenesis, programmed cell death, and inflammatory response.  Interestingly, among the central functions of TSPO is the modulation of cell nuclear gene expression via the mitochondria to cell nucleus signaling pathway. Via this modulation of numerous cellular functions, TSPO is able to take part in homeostasis of the cell and organism, including responses to disease, injury, and stress. Thus, it is no surprise that TSPO has been shown to be involved in various diseases and injurious processes. Such disorders include neurodegenerative diseases and brain injury, in particular, the chronic progressive components of these disorders; mental and emotional disorders; cardiovascular disorders; and cancer. Therefore, TSPO has attracted attention as a potential venue amenable to the development therapeutic and diagnostic applications for various diseases. A drawback that must be overcome is that toxic side effects remain a significant barrier to the progress of TSPO ligands as therapeutic agents for the various abovementioned disorders. As TSPO expression is typically elevated in response to sickness and injury, it can also serve as a biomarker for non-invasive procedures. In conclusion, TSPO is a highly worthwhile subject for research aiming to develop treatments for the disorders it is known to be involved in, including research designed to establish resolution of the various intracellular molecular biological mechanisms whereby TSPO can regulate cellular functions.

Dr. Leo Veenman
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. 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

  • TSPO
  • brain disease and injury
  • cardiovascular disorder
  • cancer
  • mitochondrial function
  • genomics

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

15 pages, 4633 KiB  
Article
Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina
by Fahad Farhan, Mohammad Almarhoun, Aileen Wong, Amy S. Findlay, Chris Bartholomew, Mark T. S. Williams, Toby W. Hurd and Xinhua Shu
Cells 2021, 10(11), 3066; https://doi.org/10.3390/cells10113066 - 07 Nov 2021
Cited by 10 | Viewed by 2310
Abstract
Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the [...] Read more.
Cholesterol dysregulation has been implicated in age-related macular degeneration (AMD), the most common cause of visual impairment in the elderly. The 18 KDa translocator protein (TSPO) is a mitochondrial outer membrane protein responsible for transporting cholesterol from the mitochondrial outer membrane to the inner membrane. TSPO is highly expressed in retinal pigment epithelial (RPE) cells, and TSPO ligands have shown therapeutic potential for the treatment of AMD. Here, we characterized retinal pathology of Tspo knockout (KO) mice using histological, immunohistochemical, biochemical and molecular biological approaches. We found that Tspo KO mice had normal retinal morphology (by light microscopy) but showed elevated levels of cholesterol, triglycerides and phospholipids with perturbed cholesterol efflux in the RPE cells of Tspo KO mice. Expression of cholesterol-associated genes (Nr1h3, Abca1, Abcg1, Cyp27a1 and Cyp46a1) was significantly downregulated, and production of pro-inflammatory cytokines was markedly increased in Tspo KO retinas. Furthermore, microglial activation was also observed in Tspo KO mouse retinas. These findings provide new insights into the function of TSPO in the retina and may aid in the design of new therapeutic strategies for the treatment of AMD. Full article
(This article belongs to the Special Issue Advances in translocator protein (TSPO) research)
►▼ Show Figures

Graphical abstract

17 pages, 4136 KiB  
Article
Neurogenic Potential of the 18-kDa Mitochondrial Translocator Protein (TSPO) in Pluripotent P19 Stem Cells
by Laura González-Blanco, Juan Carlos Bermejo-Millo, Gabriela Oliveira, Yaiza Potes, Eduardo Antuña, Iván Menéndez-Valle, Ignacio Vega-Naredo, Ana Coto-Montes and Beatriz Caballero
Cells 2021, 10(10), 2784; https://doi.org/10.3390/cells10102784 - 17 Oct 2021
Cited by 5 | Viewed by 2578
Abstract
The 18-kDa translocator protein (TSPO) is a key mitochondrial target by which different TSPO ligands exert neuroprotective effects. We assayed the neurogenic potential of TSPO to induce the neuronal differentiation of pluripotent P19 stem cells in vitro. We studied changes in cell morphology, [...] Read more.
The 18-kDa translocator protein (TSPO) is a key mitochondrial target by which different TSPO ligands exert neuroprotective effects. We assayed the neurogenic potential of TSPO to induce the neuronal differentiation of pluripotent P19 stem cells in vitro. We studied changes in cell morphology, cell proliferation, cell death, the cell cycle, mitochondrial functionality, and the levels of pluripotency and neurogenesis of P19 stem cells treated with the TSPO ligand, PK 11195, in comparison to differentiation induced by retinoid acid (RA) and undifferentiated P19 stem cells. We observed that PK 11195 was able to activate the differentiation of P19 stem cells by promoting the development of embryoid bodies. PK 11195 also induced changes in the cell cycle, decreased cell proliferation, and activated cell death. Mitochondrial metabolism was also enhanced by PK 11195, thus increasing the levels of reactive oxygen species, Ca2+, and ATP as well as the mitochondrial membrane potential. Markers of pluripotency and neurogenesis were also altered during the cell differentiation process, as PK 11195 induced the differentiation of P19 stem cells with a high predisposition toward a neuronal linage, compared to cell differentiation induced by RA. Thus, we suggest a relevant neurogenic potential of TSPO along with broad therapeutic implications. Full article
(This article belongs to the Special Issue Advances in translocator protein (TSPO) research)
►▼ Show Figures

Graphical abstract

11 pages, 3569 KiB  
Article
TSPO Expression Modulatory Effect of Acetylcholinesterase Inhibitor in the Ischemic Stroke Rat Model
by Yoo Sung Song, Sang Hee Lee, Jae Ho Jung, In Ho Song, Hyun Soo Park, Byung Seok Moon, Sang Eun Kim and Byung Chul Lee
Cells 2021, 10(6), 1350; https://doi.org/10.3390/cells10061350 - 29 May 2021
Cited by 8 | Viewed by 2413
Abstract
We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in [...] Read more.
We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option. Full article
(This article belongs to the Special Issue Advances in translocator protein (TSPO) research)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop