ArticlePloS one2018
Effects of genetic variants in the TSPO gene on protein structure and stability.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Influence of Translocator Protein (Life (Basel, Switzerland) · 2026Article
- Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.Cellular and molecular neurobiology · 2026Article
- Towards a Biologically Defined Diagnosis: Incorporating Pathophysiological Measures Into Parkinson's Disease Clinical Criteria.Parkinson's disease · 2026Review
- Deep learning-derived arterial input function for dynamic brain PET.NeuroImage · 2025Article
- Microglia matters: visualizing the immune battle in Parkinson's disease.The Journal of clinical investigation · 2025Article
- Cholesterol-dependent enzyme activity of human TSPO1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally suppressed people with HIV.AIDS (London, England) · 2025Article
- SIFD-associated TRNT1 deficiency unveils importance of TSPO during macrophage antibacterial and antiviral responses.Frontiers in immunology · 2025Article
- Article
- 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
- Inflammation and immune dysfunction in Parkinson disease.Nature reviews. Immunology · 2022Review
- Differential mitochondrial protein interaction profile between human translocator protein and its A147T polymorphism variant.PloS one · 2022Article
- The Translocator Protein (Cancers · 2021Article
- Cancer-associated cells release citrate to support tumour metastatic progression.Life science alliance · 2021Article
- Microglia as therapeutic targets after neurological injury: strategy for cell therapy.Expert opinion on therapeutic targets · 2021Review
- Concentration, distribution, and influence of aging on the 18 kDa translocator protein in human brain: Implications for brain imaging studies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Isoform-resolved correlation analysis between mRNA abundance regulation and protein level degradation.Molecular systems biology · 2020Article
- Insight into the Structural Features of TSPO: Implications for Drug Development.Trends in pharmacological sciences · 2020Review
- Characterization of the High-Affinity Drug Ligand Binding Site of Mouse Recombinant TSPO.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 18 kDa translocator protein (TSPO) is an evolutionary conserved cholesterol binding protein localized in the outer mitochondrial membrane. Expression of TSPO is upregulated in activated microglia in various neuroinflammatory, neurodegenerative, and neoplastic disorders. Therefore, TSPO radioligands are used as biomarkers in positron emission tomography (PET) studies. In particular, a common A147T polymorphism in the TSPO gene affects binding of several high affinity TSPO radioligands. Given the relevance of TSPO as a diagnostic biomarker in disease processes, we systematically searched for mutations in the human TSPO gene by a wide array of evolution and structure based bioinformatics tools and identified potentially deleterious missense mutations. The two most frequently observed missense mutations A147T and R162H were further analysed in structural models of human wildtype and mutant TSPO proteins. The effects of missense mutations were studied on the atomic level using molecular dynamics simulations. To analyse putative effects of A147T and R162H variants on protein stability we established primary dermal fibroblast cultures from wt and homozygous A147T and R162H donors. Stability of endogenous TSPO protein, which is abundantly expressed in fibroblasts, was studied using cycloheximide protein degradation assay. Our data show that the A147T mutation significantly alters the flexibility and stability of the mutant protein. Furthermore both A147T and R162H mutations decreased the half-life of the mutant proteins by about 25 percent, which could in part explain its effect on reduced pregnenolone production and susceptibility to neuropsychiatric disorders. The present study is the first comprehensive bioinformatic analysis of genetic variants in the TSPO gene, thereby extending the knowledge about the clinical relevance of TSPO nsSNPs.
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