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, 53 (1), 20-27

Translocator Protein (TSPO): The New Story of the Old Protein in Neuroinflammation

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Translocator Protein (TSPO): The New Story of the Old Protein in Neuroinflammation

Younghwan Lee et al. BMB Rep.

Abstract

Translocator protein (TSPO), also known as peripheral benzodiazepine receptor, is a transmembrane protein located on the outer mitochondria membrane (OMM) and mainly expressed in glial cells in the brain. Because of the close correlation of its expression level with neuropathology and therapeutic efficacies of several TSPO binding ligands under many neurological conditions, TSPO has been regarded as both biomarker and therapeutic target, and the biological functions of TSPO have been a major research focus. However, recent genetic studies with animal and cellular models revealed unexpected results contrary to the anticipated biological importance of TSPO and cast doubt on the action modes of the TSPO-binding drugs. In this review, we summarize recent controversial findings on the discrepancy between pharmacological and genetic studies of TSPO and suggest some future direction to understand this old and mysterious protein. [BMB Reports 2020; 53(1): 20-27].

Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicting interests.

Figures

Fig. 1
Fig. 1
Sequence alignment of eukaryotic TSPO homologues. (A) TSPO has a highly conserved sequence, especially on transmembrane domains from plants to human. (B) TSPO topology in the mitochondrial membrane.
Fig. 2
Fig. 2
Differences between human and rodent TSPO. Unlike the positive correlation between TSPO and neuroinflammation in rodents, TSPO expression in human is not related to inflammation level. Binding partners of TSPO ligands are also different between the two species. For instance, PK11195 has a binding affinity to human CAR but not to mouse CAR.

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