Current Pharmaceutical Design - Volume 17, Issue 2, 2011

The glutamatergic system is involved in a wide range of physiological processes in the brain, and its dysfunction plays an important role in the etiology and pathophysiology of psychiatric disorders, including schizophrenia. Among the glutamate receptors, metabotropic glutamate receptors (mGlu receptors) have emerged as attractive therapeutic targets for the development of novel interventions for psychiatric disorders. A Read More

D-Amino acid oxidase (DAAO) catalyzes the oxidative metabolism of D-amino acids including D-serine, a full agonist at the allosteric glycine binding site of the NMDA receptor. D-serine was reported to improve negative and cognitive symptoms of schizophrenia, symptoms poorly addressed by the standard D2 antagonist therapies. Therefore, inhibition of DAAO has gained substantial interest as an effective way to increase D-ser Read More

The hypofunction hypothesis of glutamatergic neurotransmission via N-methyl-D-aspartate (NMDA) receptors in the pathophysiology of schizophrenia suggests that increasing NMDA receptor function via pharmacological manipulation could provide a new therapeutic strategy for schizophrenia. The glycine modulatory site on NMDA receptor complex is the one of the most attractive therapeutic targets for schizoph Read More

Accumulating evidence suggests that the α7 subtype of nicotinic acetylcholine receptors (nAChRs) plays a role in the pathophysiology of schizophrenia. Deficits in auditory P50 evoked potential suppression in patients with schizophrenia are associated with decreased density of α7 nAChRs in the brain. Some agonists (e.g., DMXB-A and tropisetron) at α7 nAChRs can improve P50 deficits in patients with schizophrenia Read More

The disturbance of the dopaminergic neurotransmission is a key-feature in the neurobiology of schizophrenia. The interaction between the dopaminergic and the glutamatergic neurotransmission, however, attracted more notice to the glutamatergic system. Recent research focussed on factors influencing the glutamatergic neurotransmission. A pro-inflammatory immune state influences the glutamatergic neurotransmis Read More

Schizophrenia is a chronic, severe, and disabling brain disorder that affects about 1 percent of people worldwide. The manifestations of this disorder are positive symptoms (e.g., hallucinations, delusions, racing thoughts), negative symptoms (e.g., apathy, lack of emotion, poor or nonexistent social functioning), and cognitive deficits (e.g., poor executive functioning, trouble focusing or paying attention, problems wi Read More

Disturbances of the basal ganglia processes is heavily involved in schizophrenia. Phosphodiesterase 10A (PDE10A) is a basal ganglia specific hydrolase, which plays an essential role in regulating cAMP/PKA and cGMP/PKG signalling cascades by controlling the magnitude, duration and cellular location of cAMP/cGMP elevation. Biochemical and behavioral data indicate that PDE10A inhibition activates cAMP/PKA signalling Read More

The enzyme steroid 5α-reductase (S5αR) catalyzes the conversion of Δ4-3-ketosteroid precursors - such as testosterone, progesterone and androstenedione - into their 5α-reduced metabolites. Although the current nomenclature assigns five enzymes to the S5αR family, only the types 1 and 2 appear to play an important role in steroidogenesis, mediating an overlapping set of reactions, albeit with distinct chemical chara Read More

Schizophrenia is a debilitating mental disorder that afflicts about 1% of the population worldwide. Despite intensive, multifaceted research, its exact etiology remains elusive. Epidemiological data shows that when pregnant mothers experienced malnutrition or famine (e.g. the Dutch Hunger Winter of 1994-1945 and the Chinese famine of 1959-1961), the risk of schizophrenia in their children increased by two fold. This fact co Read More

Schizophrenia is one of the most disabling psychiatric conditions. Current treatments target monoamine receptors but this approach does not address the full complexity of the disorder. Here we explore the possibility of developing new anti-psychotics by targeting microRNAs (miRNAs), single stranded RNA molecules, 21-23 nucleotides in length that are not translated into proteins and regulate gene expression. The pres Read More