ArticleJournal of Alzheimer's disease : JAD2019
TSPO Ligands Boost Mitochondrial Function and Pregnenolone Synthesis.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Site and mechanism of BK channel inhibition and cerebral artery constriction by pregnenolone.Pharmacological research · 2026Article
- Photoreceptor Vulnerability to Ferroptosis: Membrane Phospholipid Peroxidation, Mitochondrial Homeostasis, and RPE-Photoreceptor Coupling.Current issues in molecular biology · 2026Review
- Article
- A multielectrode array reveals therapeutic potential of translocator protein ligands in a zebrafish model of Dravet syndrome.The Journal of pharmacology and experimental therapeutics · 2025Article
- Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence.Frontiers in cellular neuroscience · 2025Review
- Exercise Alleviates Fluoride-Induced Learning and Memory Impairment in Mice: Role of miR-206-3p and PREG.Biological trace element research · 2024Article
- Protection from oxygen-glucose deprivation by neurosteroid treatment in primary neurons and oligodendrocytes.In vitro cellular & developmental biology. Animal · 2024Article
- From Young to Old: Mimicking Neuronal Aging in Directly Converted Neurons from Young Donors.Cells · 2024Article
- Stem Cell Therapy and Thiamine Deficiency-Induced Brain Damage.Neurochemical research · 2024Review
- Chronic administration of XBD173 ameliorates cognitive deficits and neuropathology via 18 kDa translocator protein (TSPO) in a mouse model of Alzheimer's disease.Translational psychiatry · 2023Article
- Mitochondrial TSPO Promotes Hepatocellular Carcinoma Progression through Ferroptosis Inhibition and Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Pregnenolone Inhibits Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis-Role of Matrix Metalloproteinase 2 and NADPH Oxidase 1.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Comprehensive Steroidome in Complete TSPO/PBR Knockout Mice under Basal Conditions.International journal of molecular sciences · 2023Article
- Translocator protein in the rise and fall of central nervous system neurons.Frontiers in cellular neuroscience · 2023Review
- Alcohol and pregnenolone interaction on cerebral arteries through targeting of vascular smooth muscleAdvances in drug and alcohol research · 2023Article
- Targeting TSPO Reduces Inflammation and Apoptosis in an In Vitro Photoreceptor-Like Model of Retinal Degeneration.ACS chemical neuroscience · 2022Article
- Nicotinic Acetylcholine Receptors and Microglia as Therapeutic and Imaging Targets in Alzheimer's Disease.Molecules (Basel, Switzerland) · 2022Review
- Translocator Protein Ligand PIGA1138 Reduces Disease Symptoms and Severity in Experimental Autoimmune Encephalomyelitis Model of Primary Progressive Multiple Sclerosis.Molecular neurobiology · 2022Article
- Research Progress on the Role of Microglia Membrane Proteins or Receptors in Neuroinflammation and Degeneration.Frontiers in cellular neuroscience · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Translocator protein 18 kDa (TSPO) is located in the mitochondrial outer membrane and plays an important role in steroidogenesis and cell survival. In the central nervous system (CNS), its expression is upregulated in neuropathologies such as Alzheimer's disease (AD). Previously, we demonstrated that two new TSPO ligands based on an imidazoquinazolinone termed 2a and 2b, stimulated pregnenolone synthesis and ATP production in vitro. In the present study, we compared their effects to those of TSPO ligands described in the literature (XBD173, SSR-180,575, and Ro5-4864) by profiling the mitochondrial bioenergetic phenotype before and after treatment and investigating the protective effects of these ligands after oxidative injury in a cellular model of AD overexpressing amyloid-β (Aβ). Of note, ATP levels increased with rising pregnenolone levels suggesting that the energetic performance of mitochondria is linked to an increased production of this neurosteroid via TSPO modulation. Our results further demonstrate that the TSPO ligands 2a and 2b exerted neuroprotective effects by improving mitochondrial respiration, reducing reactive oxygen species and thereby decreasing oxidative stress-induced cell death as well as lowering Aβ levels. The compounds 2a and 2b show similar or even better functional effects than those obtained with the reference TSPO ligands XBD173 and SSR-180.575. These findings indicate that the new TSPO ligands modulate mitochondrial bioenergetic phenotype and protect against oxidative injury probably through the de novo synthesis of neurosteroids, suggesting that these compounds could be potential new therapeutic tools for the treatment of neurodegenerative disease.
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