Penicillin-binding proteins: evergreen drug targets.
Frère, Jean-Marie ;
in Current opinion in pharmacology (2014), 18
The penicillin-binding proteins (PBPs) are well known targets for the beta-lactam antibiotics. They continue to be a focus of interest for pharmaceutical design, as exemplified by the number of new agents ... [more ▼]
The penicillin-binding proteins (PBPs) are well known targets for the beta-lactam antibiotics. They continue to be a focus of interest for pharmaceutical design, as exemplified by the number of new agents under clinical investigation as well as novel experimental molecules. Considerable advances have been made in understanding the structure and function of this family of enzymes, through high-resolution structural studies and mechanistic studies in solution. These studies have thrown light on role of the high molecular mass PBPs in mediating beta-lactam resistance, although much work remains to be done to enable a full description of the mechanisms by which these proteins modulate their sensitivity towards beta-lactams while retaining their essential activity in cell wall biosynthesis. [less ▲]Detailed reference viewed: 12 (0 ULg)
The thymus as an obligatory intersection between the immune and neuroendocrine systems: pharmacological implications
in Current Opinion in Pharmacology (2010), 10Detailed reference viewed: 21 (9 ULg)
Current Opinion in Pharmacology, Volume 10, Issue 4, Section Immunomodulation
in Current Opinion in Pharmacology (2010), 10(Issue 4), 405-504Detailed reference viewed: 58 (6 ULg)
Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes.
Geenen, Vincent ; Mottet, Marie ; Dardenne, Olivier et al
in Current Opinion in Pharmacology (2010), 10
Before being able to react against infectious non-self antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only ... [more ▼]
Before being able to react against infectious non-self antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only in the thymus. The development of the autoimmune diabetogenic response results from a thymus dysfunction in programming central self-tolerance to pancreatic insulin-secreting islet β cells, leading to the breakdown of immune homeostasis with an enrichment of islet β-cell reactive effector T cells and a deficiency of β-cell specific natural regulatory T cells (nTregs) in the peripheral T-lymphocyte repertoire. Insulin-like growth factor 2 (IGF-2) is the dominant member of the insulin family expressed during fetal life by the thymic epithelium under the control of the autoimmune regulator (AIRE) gene/protein. The very low degree of insulin gene transcription in normal murine and human thymus explains why the insulin protein is poorly tolerogenic as evidenced in many studies, including the failure of all clinical trials that have attempted immune tolerance to islet β cells via various methods of insulin administration. Based on the close homology and cross-tolerance between insulin, the primary T1D autoantigen, and IGF-2, the dominant self-antigen of the insulin family, a novel type of vaccination, so-called “negative/tolerogenic self-vaccination”, is currently being developed for prevention and cure of T1D. If this approach were found to be effective for reprogramming immunological tolerance in T1D, it could pave the way for the design of other self-vaccines against autoimmune endocrine diseases, as well as other organ-specific autoimmune diseases. [less ▲]Detailed reference viewed: 50 (17 ULg)