Novel directions in antipsychotic target identification using gene arrays

Current Drug Targets. CNS and Neurological Disorders
Michael G PalfreymanC Anthony Altar

Abstract

Schizophrenia is a major health problem that affects 2 million individuals in the United States. Antipsychotics offer considerable symptomatic relief and, although commonly discovered by screening with single biological targets, most interact with multiple receptors and signaling pathways. Considerable evidence from family and twin studies demonstrates genetic components and multiple chromosomal regions associated with schizophrenia. The polygenic nature of schizophrenia and multiple mechanisms for most effective agents indicate the need for broader approaches to target identification. Gene expression profiling of post-mortem human brain tissue simultaneously reveals the expression of many thousands of genes. A comparison of tissue from normals and patients provides a 'disease signature' of aberrantly expressed genes. 'Drug signatures' are the gene expression changes of cultured human or animal neurons treated with psychiatric drugs, and from animals chronically treated with these drugs. A selection of genes from disease and drug signatures can create a set of targets whose changes may better predict disease and its treatment by effective agents. This multi-parameter high throughput screening (MPHTS(SM)) approach evaluates the ...Continue Reading

Citations

Oct 17, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·C Anthony AltarStephen D Ginsberg
Feb 21, 2006·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Gerard Marek, Kalpana Merchant
Sep 28, 2010·Annual Review of Pharmacology and Toxicology·John A Allen, Bryan L Roth
Jun 27, 2015·Pharmacogenomics·Hooman MirzakhaniHenk-Jan Guchelaar
Sep 18, 2007·The International Journal of Neuropsychopharmacology·Min-Chih ChengChia-Hsiang Chen
Nov 14, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yuanyuan ChenKrzysztof Palczewski
Nov 13, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Mao-Liang Chen, Chia-Hsiang Chen
Apr 3, 2004·Nature Reviews. Drug Discovery·Bryan L RothWesley K Kroeze
Apr 21, 2010·Experimental Biology and Medicine·Veronica MariottiSilvia Pellegrini

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