Diazepam binding inhibitor (DBI)

Diazepam binding inhibitor (DBI), also known as Acyl-CoA-binding protein (ACBP), is a multifunctional 10 kDa protein that plays critical roles in both the central nervous system and peripheral tissues (1.2.3, 1.5.1). In the brain, DBI and its cleavage products, known as endozepines, act as endogenous ligands for the benzodiazepine binding site of the GABA-A receptor, typically functioning as negative allosteric modulators that regulate neuronal excitability, anxiety, and seizure activity (1.3.1, 1.4.1). Peripherally, DBI serves as an intracellular carrier for long-chain acyl-CoA esters and interacts with the translocator protein (TSPO) to facilitate mitochondrial steroidogenesis (1.4.2, 1.5.1). Recent research has identified DBI as a potent extracellular inhibitor of autophagy and a regulator of appetite, with its levels increasing in response to starvation and chronic overnutrition (1.1.4, 1.1.5). Elevated plasma concentrations of DBI are strongly associated with obesity, aging, and a higher risk of developing various cancers, including breast and lung cancer (1.1.2, 1.1.3). Because of its role in suppressing autophagy and promoting adipogenesis, DBI is considered a metabolic checkpoint protein (1.1.1). Therapeutic strategies currently under investigation include the use of neutralizing monoclonal antibodies to restore autophagy and improve metabolic health or anti-tumor immunity (1.1.2, 1.2.5).

Other names

Acyl-CoA-binding proteinACBPEndozepineEPAcyl-CoA-binding domain-containing protein 1ACBD1Cholecystokinin-releasing peptideCCK-RP

Competitive inhibition of the benzodiazepine binding site on GABA-A receptors; Neutralization of extracellular protein to promote autophagy and metabolic homeostasis.