更新于：2024-11-01

DBI

更新于：2024-11-01

基本信息

别名

ACBD1、ACBP、Acyl-CoA-binding protein

+ [5]

简介

Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD) recognition site located on the GABA type A receptor. It is therefore possible that this protein also acts as a neuropeptide to modulate the action of the GABA receptor.

关联

项与 DBI 相关的药物

WO2023152637

专利挖掘

靶点

DBI

作用机制-

在研机构

Assistance Publique des Hôpitaux de Paris SA [+1]

原研机构

Sorbonne Université [+2]

在研适应症

消化系统疾病 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 DBI 相关的临床结果

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100 项与 DBI 相关的转化医学

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0 项与 DBI 相关的专利（医药）

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587

项与 DBI 相关的文献（医药）

2024-12-31·OncoImmunology

Benzodiazepines compromise the outcome of cancer immunotherapy

Article

作者: Chen, Hui ; Martins, Isabelle ; Routy, Bertrand ; Messaoudene, Meriem ; Kroemer, Guido ; Lambertucci, Flavia ; Montégut, Léa ; Derosa, Lisa ; Zitvogel, Laurence

Acyl CoA binding protein (ACBP, which is encoded by diazepam binding inhibitor, DBI) acts on the gamma-amino butyric acid (GABA) receptor type A via a specific binding site that is shared by diazepam and other benzodiazepines. Both ACBP/DBI and benzodiazepines act as positive allosteric modulators, hence increasing GABA effects on this receptor. Recently, we found that ACBP/DBI acts as an endogenous immunosuppressor, meaning that its antibody-mediated neutralization has immunostimulatory effects and enhances the efficacy of immunotherapy and chemoimmunotherapy in mouse models. Driven by these considerations, we investigated whether diazepam administration in mice would reverse the beneficial effects of ACBP/DBI neutralization on cancer chemoimmunotherapy. Indeed, diazepam abolished the therapeutic of anti-ACBP/DBI antibodies, supporting the idea that diazepam exerts immunosuppressive properties. Of note, treatment with benzodiazepines was associated with poor clinical responses to chemoimmunotherapy in patients with non-small cell lung cancer (NSCLC) as compared to individuals not receiving any psychotropic drugs. Medication with other psychotropic drugs than benzodiazepines did not compromise the outcome of chemoimmunotherapy, indicating that this immunosuppressive effect was benzodiazepine specific. We conclude that benzodiazepines may confer systemic immunosuppression. This hypothesis requires further epidemiological and clinical confirmation.

2024-08-15·Journal of Clinical Investigation

Peripheral gating of mechanosensation by glial diazepam binding inhibitor

Article

作者: Hao, Han ; Mullen, Pierce ; Lee, Sang Hoon ; Shah, Shihab ; Berta, Temugin ; Prato, Vincenzo ; Maffei, Benito ; Gamper, Nikita ; Du, Xiaona ; Guo, Xianchuan ; Prudente, Arthur Silveira ; Tonello, Raquel ; Jones, Frederick ; Li, Xinmeng ; Wang, Yujin ; Figoli, Sofia

We report that diazepam binding inhibitor (DBI) is a glial messenger mediating crosstalk between satellite glial cells (SGCs) and sensory neurons in the dorsal root ganglion (DRG). DBI is highly expressed in SGCs of mice, rats, and humans, but not in sensory neurons or most other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without major effects on other sensory modalities. In vivo overexpression of DBI in SGCs reduces sensitivity to mechanical stimulation and alleviates mechanical allodynia in neuropathic and inflammatory pain models. We further show that DBI acts as an unconventional agonist and positive allosteric modulator at the neuronal GABAA receptors, particularly strongly affecting those with a high-affinity benzodiazepine binding site. Such receptors are selectively expressed by a subpopulation of mechanosensitive DRG neurons, and these are also more enwrapped with DBI-expressing glia, as compared with other DRG neurons, suggesting a mechanism for a specific effect of DBI on mechanosensation. These findings identified a communication mechanism between peripheral neurons and SGCs. This communication modulates pain signaling and can be targeted therapeutically.

2024-08-14·Science Translational Medicine

Acyl-CoA binding protein for the experimental treatment of anorexia

Article

作者: Maiuri, Maria Chiara ; Pan, Yuhong ; Pan, Hui ; Mailliet, Francois ; Lachkar, Sylvie ; Nogueira-Recalde, Uxía ; Oury, Franck ; Cerone, Alexandra ; Joseph, Adrien ; Stoll, Gautier ; Moriceau, Stéphanie ; Derosa, Lisa ; Li, Sijing ; Tolle, Virginie ; Anagnostopoulos, Gerasimos ; Ramoz, Nicolas ; Marmorino, Federica ; Gouveia, Zelia L. ; Cremolini, Chiara ; Gorwood, Philip ; Bourgin, Mélanie ; Dardennes, Roland ; Kepp, Oliver ; Duriez, Philibert ; Motiño, Omar ; Aprahamian, Fanny ; López-Otín, Carlos ; Zitvogel, Laurence ; Lambertucci, Flavia ; Sauvat, Allan ; Martins, Isabelle ; Carbonnier, Vincent ; Perez, Franck ; Montégut, Léa ; Alves Costa Silva, Carolina ; Boedec, Erwan ; Mao, Misha ; Chen, Hui ; Durand, Sylvère ; Kroemer, Guido

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.