2. TSPO ligands

Ligands, either endogenous or synthetic, to TSPO, such as protoporphyrin IX (PPIX), PK 11195, Ro5–4864, FGIN-1-27, induce different effects on metabolism and protein expression in human well-differentiated metabolically active cells. For example, Ro5–4864, FGIN-1-27 and PPIX cause similar effects, for example, reducing cellular [18F]-fluorodeoxyglucose ([18F]-FDG) incorporation and parallel decrease in ATP generation [6–8]. The cellular effects of PK 11195 show protective attempts for cellular "detoxification" by increasing the cellular mitochondrial mass (Figure 1) [5].

In general, most of the TSPO ligands affect the cellular function or metabolism in the same general direction, but different specific TSPO ligands have their own unique effects in human cells. Regulation of gene expression via the actions of TSPO ligands on the mitochondrial TSPO may form an essential mechanism for the regulation of cellular functions.

overall TSPO expression is low, and TSPO is mainly found in glia and at very low levels in neurons [9]. But in the abnormal brain, TSPO is mainly expressed in glia, some hypertrophic

Figure 1. A: Microscopic image of cells stained by Mitotracker green stain (MTG). Strings of green stained mitochondria are apparent. Confocal microscopy, scale – 20 μ. B: Flow cytometry of cells stained by MTG. The histogram of the mitochondrial mass is shifted showing when exposed to PK 11195 (10<sup>5</sup> M) indicating on increase in the mitochondrial

18 kDa Translocator Protein in Mitochondria-Related Pathology: The Case of Traumatic Brain Injury

http://dx.doi.org/10.5772/intechopen.74057

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TSPO expression is upregulated in the injured brain and topographically localized in the inflamed areas. Additionally, in various neuropathologies, that is, gliomas, ischemia, viral encephalitis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis), local high expression of TSPO is

Mitochondria are the key regulators of cell survival and death. Mitochondria interact with numerous specific proteins, which are involved in genetic forms of neurodegenerative diseases [5, 9, 11]. When TSPO is a mitochondrial protein, it plays an important role in various cellular

The potential intracellular mechanisms related to TSPO include Ca++ release, ATP production, reactive oxygen species (ROS) generation, and cytochrome C release from the mitochondria in

astrocytes, infiltrating macrophages, and at low levels in neurons.

pathways related to brain damage and neurodegenerative disease [12].

relation to programmed cell death [7, 13, 14].

mass in comparison with the unexposed control.

evident [9–11, 12].

The exact mode of action of the specific TSPO ligands is not clear enough and should be further investigated. Due to the evidence of the nonuniform response of cells to the different specific ligands, an attempt to elucidate the role of the TSPO in cellular metabolism and modulation of cell phenotype should be promoted.
