| Autor: |
Korth, Carsten, Bradshaw, Nicholas J., Bader, Verian, Trossbach, Svenja V., Marreiros, Rita, Ottis, Philipp, Li, Ka Wan, Smit, August B., Hennah, William |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
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| Popis: |
Background: In postmitotic neurons protein homeostasis is a critical issue, with disturbances such as in chronic mental illnesses (CMI) resulting in either subtle or more extensive accumulation of insoluble proteins. The goal of our research is to identify unique signatures of insoluble proteins associated with CMI for biologically definined diagnoses. Methods: The insoluble proteome of post mortem brains from patients with mental illnesses (SMRI Consortium Collection, Baltimore, USA) was purified as described (2008 J Neurosci 28:3839-45 ; 2013 PloS ONE 8: e75112). The insoluble proteome was investigated by three methods: 1. presence of candidate proteins such as Disrupted-in-Schizophrenia 1 (DISC1), 2. Epitope discovery by antibody generation after immunizing with insoluble proteome from pooled post mortem schizophrenia brains 3. Quantitative proteomics of the insoluble proteome. Results: Insoluble DISC1 protein was identified in approximately 15% of cases with mental illness, coaggregating with other proteins associated with mental illness such as dysbindin. Epitope discovery led to the discovery of CRMP1 and TRIOBP-1 that change their assembly state in mental illness conditions. Quantitative proteomics of pooled insoluble proteomes from patients (n = 15 each) with schizophrenia, bipolar disorder, depression or non-illness controls yielded unique signatures of insoluble proteins. Conclusions: The identification of insoluble protein assemblies in chronic mental illnesses has 1. Confirmed or extended the significance of mental illness candidate genes like DISC1, 2. Led to the identification of novel candidate proteins like CRMP1, TRIOBP-1, 3. aberrant proteostatic signatures point to distinct disturbances in cellular machinery and cellular pathology presenting valuable pharmacological targets. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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