The translocator protein (18Â kDa) and its role in neuropsychiatric disorders

Article ID	Journal	Published Year	Pages	File Type
7302235	Neuroscience & Biobehavioral Reviews	2017	68 Pages	PDF

Abstract

Translocator protein (TSPO) is an 18Â kDa translocator membrane protein expressed in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. TSPO is involved in cellular functions, including the regulation of cell proliferation, transport of cholesterol to the inner mitochondrial membranes of glial cells, regulation of mitochondrial quality control, and haem synthesis. In the brain, TSPO has been extensively used as a biomarker of injury and inflammation. Indeed, TSPO was up-regulated in several inflammatory and neurodegenerative diseases. In contrast, the expression of TSPO was decreased in peripheral blood from psychiatric patients. Since TSPO is involved in several mechanisms related to mitochondrial function and inflammatory alterations, therapeutic approaches focusing on the regulation of TSPO may provide a new avenue for the treatment of neuropsychiatric disorders. Based on the involvement of mitochondrial alterations in the neurobiology of neuropsychiatric disorders, this review will focus on the functions and physiological roles of TSPO and the potential of TSPO ligands as therapeutic strategies for the treatment of neuropsychiatric disorders.

Keywords

APAf-1 PKCε GSP mRNA CuS TSPO ASC VDAC THDOC PAMPs OCD IAP NMDAR AP-1 MPTP ANT ETs iNOS 3β-HSD IL-1β LPS 3α-HSD PK 11195 Ro5-4864 NIX PINK-1 ERK-1/2 tetrahydrodeoxycorticosterone SMAC sequestosome 1 CCL2 SULT RAF-1 P450scc NLR DAMPs STAT-3 3α-hydroxysteroid dehydrogenase 4′-chlorodiazepam DNA MAPK ROS Adenosine Triphosphate ATP AIF post-traumatic stress disorder PTSD bipolar disorder obsessive-compulsive disorder neuropsychiatric disorders chronic unpredictable stress deoxyribonucleic acid Neuroinflammation damage-associated molecular patterns pathogen-associated molecular patterns mitochondrial permeability transition pore Interleukin-1β Alzheimer’s disease Parkinson’s disease Generalized social phobia adenine nucleotide translocator tumour necrosis factor-α Positron emission tomography caspase-recruitment domain CNS Second mitochondria-derived activator of caspase messenger ribonucleic acid Star central nervous system apoptosis inducing factor TNF-α lipopolysaccharide Signal transducer and activator of transcription-3 inhibitor of apoptosis protein Multiple sclerosis Nitric oxide human immunodeficiency virus HIV Parkin PANDAS PET translocator protein Steroidogenic acute regulatory protein activator protein 1 Pten voltage dependent anion channel chemokine (C-C motif) ligand 2 mitogen-activated protein kinases extracellular signal-regulated kinase-1/2 GABAA Reactive oxidative species N-methyl-d-aspartate receptor NOD-like receptors