ArticleJournal of neuroendocrinology2020
Mitochondria modulatory effects of new TSPO ligands in a cellular model of tauopathies.
Article in Journal of neuroendocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Current advances in the structure-activity relationship (SAR) analysis of the old/new 18-kDa translocator protein ligands.Molecular diversity · 2025Review
- Functional Analysis of Direct In Vitro Effect of Phosphorylated Tau on Mitochondrial Respiration and Hydrogen Peroxide Production.Biomolecules · 2025Article
- Inflammaging and Brain Aging.International journal of molecular sciences · 2024Review
- ER-mitochondria contacts and cholesterol metabolism are disrupted by disease-associated tau protein.EMBO reports · 2023Article
- Genetically Engineered TripleCells · 2023Article
- Spermidine Rescues Bioenergetic and Mitophagy Deficits Induced by Disease-Associated Tau Protein.International journal of molecular sciences · 2023Article
- Inflammation in multiple system atrophy.Frontiers in immunology · 2023Review
- Translocator protein in the rise and fall of central nervous system neurons.Frontiers in cellular neuroscience · 2023Review
- Targeting TSPO Reduces Inflammation and Apoptosis in an In Vitro Photoreceptor-Like Model of Retinal Degeneration.ACS chemical neuroscience · 2022Article
- The 18-kDa Translocator Protein PET Tracers as a Diagnostic Marker for Neuroinflammation: Development and Current Standing.ACS omega · 2022Review
- Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy.Journal of neuroinflammation · 2021Article
- Article
- Review
- Insights into Disease-Associated Tau Impact on Mitochondria.International journal of molecular sciences · 2020Review
- Perspectives for New and More Efficient Multifunctional Ligands for Alzheimer's Disease Therapy.Molecules (Basel, Switzerland) · 2020Review
- Steroids and Alzheimer's Disease: Changes Associated with Pathology and Therapeutic Potential.International journal of molecular sciences · 2020Review
- Review
- Honeybush Extracts (Oxidative medicine and cellular longevity · 2020Article
- Mitochondria modulatory effects of new TSPO ligands in a cellular model of tauopathies.Journal of neuroendocrinology · 2020Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Translocator protein 18 kDa (TSPO) is a mitochondrial protein located in the outer membrane and involved in cholesterol translocation, a prerequisite for steroid biosynthesis. TSPO modulation also appears to play a role in other mitochondrial functions, including mitochondrial respiration and cell survival. In the central nervous system, its expression is up-regulated in neuropathology such as Alzheimer's disease (AD). Previously, we demonstrated that two new TSPO ligands, named 2a and 2b, stimulated pregnenolone synthesis and ATP production in a cellular model of AD overproducing β-amyloid peptide. The present study aimed to evaluate the impact of the new TSPO ligands on mitochondrial dysfunction in a cellular model of AD-related tauopathy (human neuroblastoma cells SH-SY5Y stably overexpressing the P301L-mutant Tau) presenting mitochondrial impairments, including a decreased ATP synthesis and mitochondrial membrane potential, as well as a decrease in pregnenolone synthesis compared to control cells. The effects of our new ligands were compared with those of TSPO ligands described in the literature (XBD173, SSR-180,575 and Ro5-4864). The TSPO ligands 2a and 2b exerted beneficial mitochondrial modulatory effects by increasing ATP levels and mitochondrial membrane potential, paralleled by an increase of pregnenolone levels in mutant Tau cells, as well as in control cells. The compounds 2a and 2b showed effects on mitochondrial activity similar to those obtained with the TSPO ligands of reference. These findings indicate that the new TSPO ligands modulate the mitochondrial bioenergetic phenotype as well as the de novo synthesis of neurosteroids in a cellular model of AD-related tauopathy, suggesting that these compounds could be potential new therapeutic tools for the treatment of AD.
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