Table of Contents

April 2006; 6 (2)


Nascent Transcripts


  • Prostaglandins (PG) are synthesized by the sequential action of phosholipases, cyclooxygenases (COX)-1 and COX-2, and specific terminal synthases, and exert their diverse biological effects through several membrane receptors. In particular, PGE2 is involved in many normal and pathological pathways that are mediated by four different E prostanoid receptors (EP1–4). Selective COX-2 inhibitors (Coxibs) have analgesic and antipyretic effects that are indistinguishable from those of nonsteroidal anti-inflammatory drugs (NSAIDs), but some possess hazardous cardiovascular side effects. Recent results indicate that EP1 and EP4 antagonists might prove useful for inhibiting the unwanted actions of COX-2. Has the time come for research to examine earnestly the selective antagonism of EP subtypes rather than further the development of direct COX-2 inhibitors?

  • The accumulation of amyloid-β peptides in the brain is a major factor of Alzheimer Disease. Central to the production of the amyloid-β peptides are the proteolytic secretases, which, recently, have been important targets of drug discovery. Newly published results indicate that the sorting protein-related receptor sorLA/LR11 regulates processing and trafficking of the precursor of the amyloid-β peptides, revealing an alternative target for developing molecular clinical therapeutic compounds for Alzheimer Disease.


  • Since the original description of the histamine H3 receptor as a presynaptic autoreceptor that inhibits histamine release, there has been considerable effort to develop potent and selective H3 receptor antagonists for the potential treatment of a variety of disorders affecting cognition (Attention Deficit Hyperactivity Disorder, Alzheimer Disease, and schizophrenia), sleep (hypersomnia and narcolepsy), and homeostasis (obesity). We review some of the preclinical considerations, from both an H3 receptor biology as well as a more general drug discovery perspective, that need to be taken into account in developing effective H3 receptor antagonists for the treatment of these diseases.

  • Iron is essential for brain function but its accumulated excess is harmful. Elevated iron concentrations in specific brain regions have been associated with many neurodegenerative disorders, but its contribution to neurodegeneration has been controversial. This review discusses some recently identified mutations in proteins responsible for maintaining cellular iron homeostasis, revealing the critical role of iron dysregulation in neurodegeneration.

  • Vascular endothelial cells represent both a clinically important target and barrier for the delivery of therapeutics. This review discusses drug delivery systems (DDS) that can be used to target drugs to, into, and across endothelial cells. Specific attention is given to cellular (e.g., endothelial cell–surface molecules and the targeting of drugs to subcellular compartments), molecular (e.g., molecular design of recombinant fusion proteins and other targeting systems), and bioengineering (e.g., synthesis of biocompatible nanocarriers) aspects in the successful design of DDS that translocate therapeutic enzymes to endothelial cells.

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