CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 11, Issue 6, 2012

The role of A1 and A3 receptors is discussed based on data almost exclusively obtained in the hippocampus. This brain area, where A1 receptor expression predominates, has been a matter of intensive research in the adenosine field. Interestingly, in the last decade, the relevance of the much less expressed adenosine receptor in the hippocampus, the A2A receptor, has been put forward. These two high affinity receptors Read More

Adenosine A2B and, much more importantly, adenosine A2A receptors modulate many physiological and pathological processes in the brain. In this review, the most recent evidence concerning the role of such receptors and their potential therapeutic relevance is discussed. The low affinity of A2B receptors for adenosine implies that they might represent a good therapeutic target, since they are activated only under pathologic Read More

P2X receptors are homo- or heterotrimeric ATP-gated cation channels that assemble from seven subunits, P2X1-P2X7. To our knowledge, no drug that acts on the P2X1 or P2X2 receptors in the CNS or elsewhere in the body has been approved, nor is there such a drug currently in clinical trials. Only a few non-drug-like antagonists such as the suramin derivatives NF449 and NF770 and the anthraquinone derivative PSB-1011 are Read More

The strong expression of ATP-gated P2X3 receptors by a subpopulation of sensory neurons indicates the important role of these membrane proteins in nociceptive signaling in health and disease, especially when the latter is accompanied by chronic pain syndromes. Molecular and cell biology studies have shown that these receptors exist mainly as trimeric homomers, and, in part, as heteromers (assembly of two P2X3 Read More

We have learned various data on the role of purinoceptors (P2X4, P2X7, P2Y6 and P2Y12 receptors) expressed in spinal microglia and several factors that presumably activate microglia in neuropathic pain after peripheral nerve injury. Especially P2X4 receptors (P2X4Rs) make a critical contribution to the pain processing. P2X4Rs of microglia might be promising targets for treating neuropathic pain. A predicted therapeut Read More

Purine nucleotides are well established as extracellular signaling molecules. P2X7 receptors (P2X7Rs) are members of the family of ionotropic ATP-gated receptors. Their activity can be found in a limited number of cell types, but is readily detectable in cells of hemopoietic lineage including macrophages, microglia, and certain lymphocytes, and mediates the influx of Ca2+ and Na+ as well as the release of pro-inflammatory Read More

P2Y receptors for extracellular nucleotides are coupled to activation of a variety of G proteins and stimulate diverse intracellular signaling pathways that regulate functions of cell types that comprise the central nervous system (CNS). There are 8 different subtypes of P2Y receptor expressed in cells of the CNS that are activated by a select group of nucleotide agonists. Here, the agonist selectivity of these 8 P2Y receptor subtype Read More

Extracellular nucleotide and nucleoside are signaling molecules with a wide range of actions in the central nervous system (CNS). Extracellular ATP is released by several mechanisms involving ATP binding cassette transporters, hemichannels, P2X7 receptors, or volume-sensitive chloride channels. The levels of ATP and its hydrolysis product, adenosine, in the synaptic cleft are controlled by a complex cascade of cell surfac Read More

While ATP is recognized as an intracellular energy source for many biochemical reactions, it is now recognised it is also an important extracellular signalling molecule. ATP is involved in both physiological and pathological events in most cell types, and receptor subtypes have been cloned and characterised. An important goal of purinergic research today is to annotate the human genome with functional information regarding t Read More

Nurr1 is a member of the nuclear receptor superfamily and is a potential susceptibility gene for Parkinson’s disease (PD). Several lines of studies in vitro and in vivo reported that defects in the Nurr1 gene cause nigrostriatal neuronal deficiency as seen in PD. In the present study, we used a a synthetic low molecular weight Nurr1 activator which increases the transcription of Nurr1 to investigate whether it has anti-parkinsonian Read More

This study explores the ability of a catalytic antioxidant, Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), to protect against neuronal and glial oxidative stress and death after spinal cord injury (SCI). Nine different doses of MnTBAP were administered into the intrathecal space of the rat spinal cord immediately following moderate SCI to establish dose - response curves for prevention of lipid peroxidation and neuron deat Read More

Methylene Blue (MB) is being investigated in clinical studies for its beneficial effects in the treatment of Alzheimer disease. However, its exact mechanisms of action have not been fully elucidated. The modulation of nicotinic acetylcholine receptors (nAChRs) has been suggested to play a role in the pathogenesis of various neurodegenerative diseases. Therefore, in the present study, the effect of MB on the function of the Read More