Translocator protein (TSPO) (TSPO)

Translocator protein (TSPO), formerly known as the peripheral benzodiazepine receptor, is an 18 kDa protein primarily localized to the outer mitochondrial membrane (UniProt P30536). In the healthy central nervous system, TSPO expression is minimal; however, it is dramatically upregulated in activated microglia and infiltrating macrophages at sites of neuroinflammatory lesions (PMID: 31263244). This specific upregulation makes TSPO the gold-standard molecular target for Positron Emission Tomography (PET) imaging to visualize and monitor neuroinflammation in diseases such as Multiple Sclerosis, Alzheimer's disease, and stroke (StatPearls: Neuroinflammation). Beyond its role as a biomarker, TSPO facilitates the translocation of cholesterol into the mitochondria, which is the rate-limiting step in the synthesis of neurosteroids that possess neuroprotective and anti-inflammatory properties (PMID: 25231065). Pharmacological targeting of TSPO aims to either image the density of activated immune cells or modulate their functional state to reduce neurotoxicity. A significant challenge in targeting TSPO is the presence of the rs6471 single nucleotide polymorphism in humans, which significantly alters the binding affinity of many therapeutic and diagnostic ligands, requiring patient stratification (PMID: 22539440).

Other names

Peripheral benzodiazepine receptorPBRMitochondrial benzodiazepine receptorBZRPTranslocator protein 18 kDaActivated microglia and macrophages in neuroinflammatory lesions

TSPO ligands bind to the 18 kDa translocator protein on the outer mitochondrial membrane of activated microglia and macrophages. These ligands are primarily used as radiotracers in Positron Emission Tomography (PET) to quantify neuroinflammation, or as therapeutic modulators to stimulate neurosteroidogenesis and shift microglial activation from a pro-inflammatory to an anti-inflammatory state (PMID: 31263244, PMID: 25231065).