Insights from Proteomic Studies on Schizophrenia Preclinical Models: What Can We Learn for Drug Discovery?

Abstract

Proteomics offers the ability to monitor and identify changes in protein expression and/or signalling pathways with high precision, accuracy and reproducibility. Proteomic techniques, including bioinformatics software, are steadily advancing, and technical improvements to the methods currently employed for protein separation and protein identification will dramatically increase the number of proteomics-based schizophrenia research studies. The advent of high-throughput techniques allows scientists to quantify complex biological mixtures, such as postmortem brain, and to identify and validate new biomarkers. Animal models have contributed much to our understanding of disease mechanisms and are often utilised in research because of their abundant supply and ease of manipulation. Different theories regarding the aetiology of schizophrenia make the design of a single schizophrenia animal model impossible. Therefore, there are many preclinical animal models for schizophrenia research, each of which has relevance to different aspects of the neurobiology of the disorder and its treatment. Preclinical animal models in schizophrenia research are vital for biomarker discovery and in the exploration of disease neurobiology. Furthermore they are central for the testing of new drugs. Animal models in this aspect have the advantage that they enable the investigation of the neurobiology of the phenomena of interest using invasive techniques that cannot be used in humans. Proteomics-based research of these preclinical models can greatly increase our understanding of schizophrenia and shape the direction of future research. Current proteomic studies have so far been insightful and point to a role for mitochondrial dysfunction, alteration in cell signalling and cytoskeletal functioning in preclinical models. Proteomic studies of antipsychotics in preclinical models are an indispensable tool for investigating underlying schizophrenia neurobiology. Current investigations have found alterations in core mitochondrial proteins and in protein synthesis and cell signalling pathways in preclinical models of schizophrenia undergoing antipsychotic treatment. Research is encouraging, and advancement with preclinical models of schizophrenia can be made with more reliable quantitative proteomic methods. Proteomic studies on preclinical models of schizophrenia are, to date, somewhat sparse, but will hopefully multiply with the establishment of better quantitative approaches.