Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders
Abstract
The translocator protein (18 kDa) (TSPO) is localized primarily in the outer mitochondrial membrane of steroid-synthesizing cells, including those in the central and peripheral nervous system. One of its main functions is the transport of the substrate cholesterol into mitochondria, a prerequisite for steroid synthesis. TSPO expression may constitute a biomarker of brain inflammation and reactive gliosis that could be monitored by using TSPO ligands as neuroimaging agents. Moreover, initial clinical trials have indicated that TSPO ligands might be valuable in the treatment of neurological and psychiatric disorders. This Review focuses on the biology and pathophysiology of TSPO and the potential of currently available TSPO ligands for the diagnosis and treatment of neurological and psychiatric disorders.
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TSPO is a peripheral benzodiazepine receptor expressed on the outer mitochondrial layer of microglia, and is believed to be upregulated during microglial activation.
“TSPO is a peripheral benzodiazepine receptor expressed on the outer mitochondrial layer of microglia, and is believed to be upregulated during microglial activation (Rupprecht et al, 2010).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Rupprecht et al, 2010
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Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
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“TSPO is an outer mitochondrial membrane protein whose role is not completely elucidated [2–5], but is purported to be implicated in a variety of cellular and mitochondrial functions, including biosynthesis of steroids and haeme, porphyrin transport, apoptosis, cell proliferation, and neuromodulation [6, 7].”
BackgroundBialer, M., Johannessen, S. I., Koepp, M. J., Levy, R. H., Perucca, E., Perucca, P., Tomson, T., & White, H. S. (2022) · Epilepsia · doi:10.1111/epi.17373 · Cited by 17 · see citing works
Wu, L.-P., Gong, Z.-F., Wang, H., Zhou, Z.-S., Zhang, M.-M., Liu, C., Ren, H.-M., Yang, J., Han, Y., & Zeng, C.-Y. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0293-x · Cited by 12 · see citing works
- Authors
- Rupprecht, R., Papadopoulos, V., Rammes, G., Baghai, T. C., Fan, J., Akula, N., Groyer, G., Adams, D., & Schumacher, M.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Research Institute of the McGill University Health Centre (CA)
- Max Planck Institute of Psychiatry (DE)
- Georgetown University Medical Center (US)
- Inserm (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Venue
- Nature Reviews Drug Discovery
- Published
- 2010-12
- Volume
- 9
- Issue
- 12
- Pages
- 971-988
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2031648971
- Cited by
- 930
- References
- 209
- Citations by year
- 2026: 20 · 2025: 38 · 2024: 74 · 2023: 54 · 2022: 57 · 2021: 78 · 2020: 81 · 2019: 53 · 2018: 86 · 2017: 69 · 2016: 65 · 2015: 79 · 2014: 56 · 2013: 50 · 2012: 41
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute of Environmental Health Sciences (R01ES007747, ES 07747)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- translocator protein (TSPO), TSPO ligands, mitochondrial steroidogenesis, cholesterol transport, neuroinflammation, reactive gliosis, anxiety, neuropathic pain, amyotrophic lateral sclerosis, neurological disorders, mental illness, therapeutic target
- MeSH terms
- Animals, Mental Disorders, Disease Models, Animal, Humans, Ligands, Nervous System Diseases, Biomarkers, Drug Delivery Systems, Receptors, GABA
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