Tspo, also known as the 18 kDa translocator protein and formerly called the peripheral benzodiazepine receptor, is an evolutionarily conserved protein located on the outer mitochondrial membrane [2,4,7]. It is involved in multiple cellular processes, such as inflammatory responses, oxidative stress, and mitochondrial homeostasis [4]. Its ligands are used as diagnostic biomarkers, and Tspo has been studied as a biomarker for neuroinflammation, especially in the context of neurodegenerative and neuropsychiatric diseases [3,4,5,6,7].

Tspo deficiency in glioma models reveals its crucial role in glioma biology. In Tspo knockout xenograft and spontaneous mouse glioma models, Tspo deficiency promoted glioma cell proliferation in vitro and glioma growth and angiogenesis in vivo. It also led to mitochondrial dysfunction, characterized by a greater number of fragmented mitochondria, decreased oxidative phosphorylation, and increased glycolysis, indicating Tspo's role in controlling the metabolic balance between these two processes [1].

In conclusion, Tspo is a key regulator in maintaining mitochondrial function and metabolic balance. Tspo knockout mouse models have demonstrated its significance in glioma growth and malignancy, highlighting its potential as a therapeutic target in glioma treatment [1].

References:

1. Fu, Yi, Wang, Dongdong, Wang, Huaishan, He, Wei, Zhang, Jianmin. . TSPO deficiency induces mitochondrial dysfunction, leading to hypoxia, angiogenesis, and a growth-promoting metabolic shift toward glycolysis in glioblastoma. In Neuro-oncology, 22, 240-252. doi:10.1093/neuonc/noz183. https://pubmed.ncbi.nlm.nih.gov/31563962/

2. Hiser, Carrie, Montgomery, Beronda L, Ferguson-Miller, Shelagh. 2021. TSPO protein binding partners in bacteria, animals, and plants. In Journal of bioenergetics and biomembranes, 53, 463-487. doi:10.1007/s10863-021-09905-4. https://pubmed.ncbi.nlm.nih.gov/34191248/

3. Salerno, Silvia, Viviano, Monica, Baglini, Emma, Da Settimo, Federico, Taliani, Sabrina. 2024. TSPO Radioligands for Neuroinflammation: An Overview. In Molecules (Basel, Switzerland), 29, . doi:10.3390/molecules29174212. https://pubmed.ncbi.nlm.nih.gov/39275061/

4. Bonsack, Frederick, Sukumari-Ramesh, Sangeetha. 2018. TSPO: An Evolutionarily Conserved Protein with Elusive Functions. In International journal of molecular sciences, 19, . doi:10.3390/ijms19061694. https://pubmed.ncbi.nlm.nih.gov/29875327/

5. Guilarte, Tomás R. 2018. TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward. In Pharmacology & therapeutics, 194, 44-58. doi:10.1016/j.pharmthera.2018.09.003. https://pubmed.ncbi.nlm.nih.gov/30189290/

6. Cumbers, Grace A, Harvey-Latham, Edward D, Kassiou, Michael, Werry, Eryn L, Danon, Jonathan J. 2024. Emerging TSPO-PET Radiotracers for Imaging Neuroinflammation: A Critical Analysis. In Seminars in nuclear medicine, 54, 856-874. doi:10.1053/j.semnuclmed.2024.09.007. https://pubmed.ncbi.nlm.nih.gov/39477764/

7. Nutma, Erik, Ceyzériat, Kelly, Amor, Sandra, Papadopoulos, Vassilios, Tournier, Benjamin B. 2021. Cellular sources of TSPO expression in healthy and diseased brain. In European journal of nuclear medicine and molecular imaging, 49, 146-163. doi:10.1007/s00259-020-05166-2. https://pubmed.ncbi.nlm.nih.gov/33433698/