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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

The Peripheral Benzodiazepine Receptor: A Promising Therapeutic Drug Target

Author(s): Sylvaine Galiegue, Norbert Tinel and Pierre Casellas

Volume 10, Issue 16, 2003

Page: [1563 - 1572] Pages: 10

DOI: 10.2174/0929867033457223

Price: $65

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Abstract

The peripheral benzodiazepine receptor (PBR) is a critical component of the mitochondrial permeability transition pore (MPTP), a multiprotein complex located at the contact site between inner and outer mitochondrial membranes, which is intimately involved in the initiation and regulation of apoptosis. PBR is a small evolutionary conserved protein, located at the surface of the mitochondria where it is physically associated with the voltage-dependent anion channel (VDAC) and adenosine nucleotide translocase (ANT) that form the backbone of MPTP. PBR is widely distributed throughout the body and has been associated with numerous biological functions. Consistent with its localization in the MPTP, PBR is involved in the regulation of apoptosis, but also in the regulation of cell proliferation, stimulation of steroidogenesis, immunomodulation, porphyrin transport, heme biosynthesis, anion transport and regulation of mitochondrial functions. The recent literature on PBR is reviewed here. Specifically, we highlight numerous results suggesting that the use of specific PBR ligands to modulate PBR activity may have potential therapeutic applications and might be of significant clinical benefit in the management of a large spectrum of different indications including cancer, auto-immune, infectious and neurodegenerative diseases. In addition, we present the proposed mechanisms by which the molecules exerted these effects, particularly oriented on the modulation of the MPTP activities.

Keywords: pbr, benzodiazepine, cancer, inflammation, arthritis


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