title: Employing proteomics to unravel the molecular effects of antipsychotics and their role in schizophrenia.
abstract: Schizophrenia is an incurable neuropsychiatric disorder managed mostly by treatment of the patients with antipsychotics. However, the efficacy of these drugs has remained only low to moderate despite intensive research efforts since the early 1950s when chlorpromazine, the first antipsychotic, was synthesized. In addition, antipsychotic treatment can produce often undesired severe side effects in the patients and addressing these remains a large unmet clinical need. One of the reasons for the low effectiveness of these drugs is the limited knowledge about the molecular mechanisms of schizophrenia, which impairs the development of new and more effective treatments. Recently, proteomic studies of clinical and preclinical samples have identified changes in the levels of specific proteins in response to antipsychotic treatment, which have converged on molecular pathways such as cell communication and signaling, inflammation and cellular growth, and maintenance. The findings of these studies are summarized and discussed in this review and we suggest that this provides validation of proteomics as a useful tool for mining drug mechanisms of action and potentially for pinpointing novel molecular targets that may enable development of more effective medications.
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Cassoli
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Aline G
authors.initials: AG
authors.lastname: Santana
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.|UNICAMP Neurobiology Center, Campinas, São Paulo, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martins-de-Souza
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000068180:Aripiprazole / Q000008:administration & dosage / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002746:Chlorpromazine / Q000008:administration & dosage / Q000009:adverse effects; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D020543:Proteome; D000068180:Aripiprazole; D003024:Clozapine; D002746:Chlorpromazine
keywords: Antipsychotics; Proteomics; Psychiatric disorders; Schizophrenia