CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 5, Issue 3, 2006

In this issue of CNS & Neurological Disorders-Drug Targets, we focus on G protein-coupled receptors (GPCRs) that are involved in regulating body weight. In six reviews, the melanocortins system (including MC4 and MC3 receptors, Agrp, MSH), the NPY receptors (including NPY-Y1, NPY-Y2, and NPY-Y5, PYY3-36), the cannabinoid system (including the development of rimonabant), the ghrelin (GHS, growth hormone secretagogue) Read More

There is overwhelming evidence that the brain melanocortin system is a key regulator of energy balance, and dysregulations in the brain melanocortin system can lead to obesity. The melanocortin system is one of the major downstream leptin signaling pathways in the brain. In contrast to leptin, preclinical studies indicate that diet-induced obese animals are still responsive to the anorectic effects of melanocorti Read More

Neuropeptide Y (NPY) is present in the hypothalamus, where it is believed to play a key role in the control of food intake. Evidence for this assertion has come from studies demonstrating that acute administration of NPY into the hypothalamus or into the brain ventricles leads to increased food intake. In the case of chronic administration, the hyperphagic effects of NPY are prolonged leading to the development of an obese stat Read More

Research into the endocannabinoid 'system' has grown exponentially in recent years, with the discovery of cannabinoid receptors and their endogenous ligands, such as anandamide and 2-arachidonoylglycerol (2-AG). Important advances have been made in our understanding of endocannabinoid transduction mechanisms, their metabolic pathways, and of the biological processes in which they are implicated. A de Read More

We evaluate the likely utility of drugs that interact, either directly or indirectly, with monoamine binding receptors for the treatment of obesity. We discuss ligands at dopaminergic, adrenergic, serotoninergic and histaminergic receptors and also drugs that either release or inhibit the reuptake of monoamine neurotransmitters. We review evidence from preclinical studies of receptor distribution and function, together with the cons Read More

Orexins were initially recognized as regulators of feeding behavior due to their exclusively production in the lateral hypothalamic area (LHA), a feeding center. Subsequently, the finding that orexin deficiency causes narcolepsy in humans and animals suggested that these hypothalamic neuropeptides play a critical role in regulating and maintaining sleep/wakefulness states. Proper maintenance of arousal during food sea Read More

Galanin is a 29/30 amino acid peptide neurotransmitter that is widely distributed throughout the central nervous system and periphery. There are three well-characterized G-protein coupled galanin receptors subtypes (GalR1-3). A more recently discovered 60 amino acid galanin-like peptide (GALP) shares amino acid sequence homology with galanin (1-13) in position 9-21 and has high binding affinity for GalR1-3, with highest Read More

The growth hormone secretagogue receptor (GHS-R) is expressed in several tissues and seems to mediate the different actions of the synthetic growth hormone secretagogues (GHS) and the endogenous ligand of this receptor, ghrelin. The GHS-R belongs to the family of G-protein coupled receptors (GPCR). Two different receptor variants, type 1a and 1b, have been described and they seem to mediate different actions in di Read More

Parkinson's disease (PD) is a progressive neurodegenerative disorder that results in major motor disturbances due primarily to loss of midbrain dopamine neurons. The mainstream treatment has been dopaminergic replacement therapy aimed at symptomatic relief, with the gold standard drug being the dopamine precursor levodopa. The general dogma has been that levodopa works primarily by indirectly activating the D Read More

The accumulation of amyloid β peptide (Aβ) is believed to be an early and critical event leading to synapse and neuronal cell loss in Alzheimer's Disease (AD). Aβ itself is toxic to neurons in vitro and the load of Aβ in vivo causes the loss of synapses and neurons in brain in animal models. Therefore, there has been considerable interest in elucidating the mechanism(s) of Aβ neurotoxicity. Here, we review the molecular sign Read More

Vitamin D is a seco-steroid hormone with multiple functions in the nervous system. Physiological brain mechanisms of vitamin D and its receptors include neuroprotection, antiepileptic effects, immunomodulation, possible interplay with several brain neurotransmitter systems and hormones, as well as the regulation of behaviours. Here we review the important role of the vitamin D neuroendocrine system in the brain, and outline Read More

Vitamin D is a seco-steroid hormone with multiple functions in the nervous system. Physiological brain mechanisms of vitamin D and its receptors include neuroprotection, antiepileptic effects, immunomodulation, possible interplay with several brain neurotransmitter systems and hormones, as well as the regulation of behaviours. Here we review the important role of the vitamin D neuroendocrine system in the brain, and outline Read More