CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 9, Issue 5, 2010

Vitamin D Links Genetic and Environmental Risk Factors in Multiple Sclerosis The risk to develop multiple sclerosis (MS) is well known to be co-defined by genetic and environmental factors. Possession of the major histocompatibility complex (MHC) allele HLA-DRB1*1501 represents by far the strongest genetic risk factor, while much smaller contributions are made by a range of other genes. Still, even this HLA-DRB1*1501 Read More

Heptahelical G protein-coupled receptors (GPCR) constitute one of the most studied groups of proteins in the genome. Intense investigation of this protein superfamily is more than justified as therapeutics targeting the GPCR superfamily account for nearly half of the current pharmacopeia. Along with many years of exemplary scientific research into the activity of GPCRs has come the creeping concept of diminishing novel s Read More

Dopamine (DA), the most abundant catecholamine in the basal ganglia, participates in the regulation of motor functions and of cognitive processes such as learning and memory. Abnormalities in dopaminergic systems are thought to be the bases for some neuropsychiatric disorders including addiction, Parkinson's disease, and Schizophrenia. DA exerts its arrays of functions via stimulation of D1-like (D1 and D5) and D2-like (D2 Read More

G protein-coupled receptors (GPCRs) are expressed throughout the nervous system where they regulate multiple physiological processes, participate in neurological diseases, and are major targets for therapy. Given that many GPCRs respond to neurotransmitters and hormones that are present in the extracellular fluid and which do not readily cross the plasma membrane, receptor trafficking to and from the plasma Read More

The neuroendocrine hormone ghrelin is an octanoylated 28-residue peptide that exerts numerous physiological functions. Ghrelin exerts its effects on the body mainly through a highly conserved G protein-coupled receptor known as the growth hormone secretagagogue receptor subtype 1a (GHS-R1a). Ghrelin and GSH-R1a are widely expressed in both peripheral and central tissues/organs, and ghrelin signaling plays a critical Read More

The G-protein coupled receptors for Δ9-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB1) and 2 (CB2) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB1 receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB2 receptors are fou Read More

Stimulation of Group I metabotropic glutamate receptors (mGluR1 and mGluR5) leads to activation of a wide variety of signalling pathways. mGluRs couple to Gαq/11 proteins, activating phospholipase Cβ1 resulting in both diacylglycerol and inositol-1,4,5- triphosphate formation followed by the activation of protein kinase C. In addition, mGluR activation can lead to modulation of a number of ion channels, such as different types Read More

A number of G-protein-coupled receptors (GPCRs) are currently under consideration as potential therapeutic targets for drugs acting in the central nervous system (CNS). Attempts to discover new medications have operated under the assumption that GPCRs are monomers and that a specific drug activates one single receptor coupled to one single signal transduction mechanism. In the neuronal membrane, GPCRs are now kn Read More

Dopamine modulation of excitatory neurotransmission is critical in the control of movement, emotion and reward. In the striatum, medium size spiny neurons (MSNs) are responsible for the integration of cortical and thalamic information that flows through parallel, partly overlapping, loops and determines adequate experience-dependent responses. Dopamine acts on MSNs through two sets of G protein-coupled receptors ( Read More

Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Althou Read More

Our understanding of the complex signaling neurophysiology of the central nervous system has facilitated the exploration of potential novel receptor-ligand system targets for disorders of this most complex organ. In recent years, many relatively neglected receptor-ligand systems have been re-evaluated with respect to their ability to potently modulate discrete tracts in the central nervous system. One such system is th Read More

Because G protein-coupled receptors (GPCRs) are numerous, widely expressed and involved in major physiological responses, they represent a relevant therapeutic target for drug discovery, particularly regarding pharmacological treatments of neurological disorders. Among the biological phenomena regulating receptor function, GPCR heteromerization is an important emerging area of interest and investigation. There is i Read More

Receptors for hormones of the hypothalamic-pituitary-gonadal axis are expressed throughout the brain. Age-related decline in gonadal reproductive hormones cause imbalances of this axis and many hormones in this axis have been functionally linked to neurodegenerative pathophysiology. Gonadotropin-releasing hormone (GnRH) plays a vital role in both central and peripheral reproductive regulation. GnRH Read More

Vasoactive intestinal peptide (VIP) is a basic 28 amino acid peptide that binds to a member of the class II family of G proteincoupled receptors (GPCRs). It is widely expressed throughout the body and plays an important role in numerous biological functions. VIP acts via three different GPCRs: VPAC1, VPAC2, and PAC1, which have been identified in various tissues, including brain, lung, kidney, gastrointestinal tract, tongu Read More