Therapeutic actions of translocator protein (18 kDa) ligands in experimental models of psychiatric disorders and neurodegenerative diseases

Arbo, Bruno Dutra; Benetti, Fernando; Garcia-Segura, Luis Miguel; Ribeiro, Mário

doi:10.1016/j.jsbmb.2015.07.007

Cited by 32 publications

(22 citation statements)

References 104 publications

(140 reference statements)

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“…The TSPO ligands have been reported as promising drugs for treatment of the various neurodegenerative diseases involving neuroinflammation [3715]. Due to the increasing interest in the pathophysiological roles of TSPO and therapeutic potential of TSPO ligands, various TSPO ligands belonging to diverse distinct chemical classes have been made [37].…”

Section: Discussionmentioning

confidence: 99%

“…Many previous studies have demonstrated that the function of TSPO is associated with anti-neuroinflammatory responses in glial cells, while a few studies reported the opposite action of TSPO [456]. Of note, the pharmacological effects of TSPO ligands were consistently immune suppressive, and therefore, have been explored as potential neurotherapeutic agents in experimental models of Alzheimer's disease (AD), depression, anxiety, multiple sclerosis, brain injuries and neuroinflammation [378]. …”

Section: Introductionmentioning

confidence: 99%

“…However, the stimulation of TLRs can also modulate neuroinflammation and produce anti-inflammatory cytokines [911]. Therefore, an increasing amount of evidence has indicated that dysregulation of TLRs and their signaling pathways may play a critical role in various neurodegenerative diseases through proand anti-inflammatory responses in microglia and astrocytes [5710]. …”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have reported the anti-inflammatory effects of TSPO ligands in microglia, but those studies on the effects of TSPO ligands and their action mechanisms were mostly limited to lipopolysaccharide (LPS, TLR4 ligand)-stimulated conditions [57]. Furthermore, the effects of the TSPO ligands are currently little known in astrocytes [3].…”

Section: Introductionmentioning

confidence: 99%

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Systematic Analysis of Translocator Protein 18 kDa (TSPO) Ligands on Toll-like Receptors-mediated Pro-inflammatory Responses in Microglia and Astrocytes

Lee

Nam

2016

Exp Neurobiol

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Translocator protein 18 kDa (TSPO) is a mitochondrial protein highly expressed on reactive microglia and astrocytes, and is considered as a biomarker for neurodegeneration and brain damage, especially neuroinflammation. Toll-like receptors (TLRs) are closely related with inflammatory responses of microglia and astrocytes and these signaling pathways regulate neuroinflammation. Previous reports have identified the anti-inflammatory effects of TSPO ligands, however study of their effects in relation to the TLR signaling was limited. Here, we investigated the effects of five representative TSPO ligands on microglia and astrocytes following activation by various TLR ligands. Our results show that TSPO ligands reduce the pro-inflammatory response elicited by the TLR ligands with more profound effects on microglia than astrocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Systematic Analysis of Translocator Protein 18 kDa (TSPO) Ligands on Toll-like Receptors-mediated Pro-inflammatory Responses in Microglia and Astrocytes

Lee

Nam

2016

Exp Neurobiol

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“…Thus, TSPO ligands have still proven efficacious in ameliorating disease pathology in numerous preclinical models and most remarkably in models bearing phenotypes in the central nervous system (24,(171)(172)(173). Recently, Ro5-4864 was shown to amend Alzheimer's disease associated phenotypes in vivo (25) by mediating positive effects in steroid hormones production (109) ( Table 3).…”

Section: The Pharmacology Of a Natural Mitochondrial Targetmentioning

confidence: 99%

TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria

Gatliff

Campanella

2016

Biochemical Journal

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The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review.

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Membrane-embedded TSPO: an NMR view

et al. 2020

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Translocator Protein (18 kDa) (TSPO) is a mitochondrial transmembrane protein commonly used as a biomarker for neuroinflammation and is also a potential therapeutic target in neurodegenerative diseases. Despite intensive research efforts, the function of TSPO is still largely enigmatic. Deciphering TSPO structure in the native lipid environment is essential to gain insight into its cellular activities and to design improved diagnostic and therapeutic ligands. Here, we discuss the influence of lipid composition on the structure of mammalian TSPO embedded into lipid bilayers on the basis of solid-state NMR experiments. We further highlight that cholesterol can influence both the tertiary and quaternary TSPO structure and also influence TSPO localization in mitochondria-associated endoplasmic reticulum membranes.

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Therapeutic actions of translocator protein (18 kDa) ligands in experimental models of psychiatric disorders and neurodegenerative diseases

Cited by 32 publications

References 104 publications

Systematic Analysis of Translocator Protein 18 kDa (TSPO) Ligands on Toll-like Receptors-mediated Pro-inflammatory Responses in Microglia and Astrocytes

Systematic Analysis of Translocator Protein 18 kDa (TSPO) Ligands on Toll-like Receptors-mediated Pro-inflammatory Responses in Microglia and Astrocytes

TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria

Membrane-embedded TSPO: an NMR view

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