This book is a printed edition of the Special Issue "Translocator Protein (TSPO)" that was published in IJMS

The high number of papers submitted and ultimately accepted for publication in this special issue attests the great amount of research being conducted on TSPO and its role in living cells. Thus, TSPO has become an extremely attractive subcellular biomark for the early detection of disease states overexpressing this protein and for the selective delivery to mitochondria of drugs and probes. Moreover, the effort in the design and synthesis of new, more specific and effective TSPO ligands proves to be very valuable. All these topics have been addressed in the special issue.

The 18 kDa translocator protein (TSPO) is an integral membrane protein known to be involved in porphyrin transport and heme biosynthesis. TSPO also plays a role in modulating immune response, regulation of cell proliferation and programmed cell death. TSPO is associated with several health conditions such as ischemic heart reperfusion, cancers and neurodegenerative diseases. While the potential of TSPO as a major therapeutic target has been well recognized, the lack of detailed understanding of its function and ligand binding sites have hindered drug design. In this thesis we will describe the expression, extraction and purification of Rhodobacter sphaeroides TSPO (RsTSPO). Rhodobacter is one of the closest ancestors of mitochondria and RsTSPO can be used as a model for mammalian TSPO. RsTSPO was overexpressed in E. coli, and it was extracted from the membranes with detergent (i.e. n-dodecylphosphocoline (DPC) and n-dodecyl-ß-D-maltoside (DDM)) then purified by Ni-affinity and size exclusion chromatographies. The RsTSPO could be expressed and purified in high yield (mg quantitites), high purity, and in its functional state. Binding studies of RsTSPO were performed utilizing fluorescence quenching of intrinsic tryptophans with a number of porphyrins ligands such as protoporphyrin IX (PPIX), hemin, meso-Tetra(4-sulfonatophenyl)porphine dihydrochloride (2HTPPS), Zn (II) meso-Terta(4-sulfonatophenyl)porphine dihydrochloride (ZnTPPS) and with the diagnostic ligand, PK11195. Binding studies of RsTSPO were performed in both detergents (DPC and DDM) to assess the effect of the membrane mimic environment on binding. We will also describe the first evidence of the catalytic activity of the purified RsTSPO under ambient light in the presence of molecular oxygen on its natural ligand, protoporphyrin IX. We will demonstrate the photodegradation of protoporphyrin IX by RsTSPO in the presence of oxygen and light. In addition, we have studied the effect of molecular oxygen and reactive oxygen scavengers (sodium azide and glutathione) on the decomposition of protoporphyrin IX. Also, we will describe preliminary NMR studies in an effort to characterize the ligand binding site(s) of TSPO. We have performed both solution and solid state NMR studies on pure RsTSPO and RsTSPO-ligand complexes.

Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most diverse and rapidly advancing fields in the life sciences. Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas. Although peripheral type benzodiazepne recognition sites have been demonstrated in the brain and peripheral organs of various species for more than 10 years, the exact physiological function or pharmacological effects have not yet been established. Peripheral benzodiazepine literature is so overwhelming that the novice may find it virtually impossible to form a clear idea about the diverse findings. This volume, dedicated exclusively to pBR and their natural and synthetic ligands, puts the available data into perspective. A truly interdisciplinary approach has brought neuroscientists, cardiologists, endocrinologists, and immunologists together to work on the description of pBR-mediated effects. The chemistry, biochemistry, and molecular biology of the pBR receptor and its ligands are reviewed, their pharmacological usefulness is conjectured, and thus a true overview of the field is provided. * SPECIAL FEATURES * This volume follows the Neuroscience Perspectives brief of providing a historical background, pharmacological, biochemical and physiological aspects of research and therapeutic potential, of its chosen topic. * The peripheral benzodiazepine recognition site has been recognised for more than ten years, but the exact physiological and pharmacological effects have not yet been established.

Plant cells house highly dynamic cytoskeletal networks of microtubules and actin microfilaments. They constantly undergo remodeling to fulfill their roles in supporting cell division, enlargement, and differentiation. Following early studies on structural aspects of the networks, recent breakthroughs have connected them with more and more intracellular events essential for plant growth and development. Advanced technologies in cell biology (live-cell imaging in particular), molecular genetics, genomics, and proteomics have revolutionized this field of study. Stories summarized in this book may inspire enthusiastic scientists to pursue new directions toward understanding functions of the plant cytoskeleton. The Plant Cytoskeleton is divided into three sections: 1) Molecular Basis of the Plant Cytoskeleton; 2) Cytoskeletal Reorganization in Plant Cell Division; and 3) The Cytoskeleton in Plant Growth and Development. This book is aimed at serving as a resource for anyone who wishes to learn about the plant cytoskeleton beyond ordinary textbooks.