engleski

Regions of proteins critical to their aggregation in mental illness

Mental illnesses are common health conditions, associated with problems functioning in family, work and social environments. These illnesses may be chronic, and they involve distress caused by changes in emotions, thoughts and/or behaviours. Examples of mental illnesses include schizophrenia, major depressive disorder, psychoses and bipolar disorder. Even though most mental illnesses patients can be treated, very little is known about their biology, their genetic component or their physiological cause. There are many possible biological mechanisms by which mental illnesses may develop, one of them being aggregation of specific proteins, which form insoluble aggregates in the brain and disrupts its correct functionality. Understanding protein aggregation may be directly linked with critical protein regions, which cause their aggregation. These critical protein regions could therefore potentially be targets for future treatment of specific mental illnesses. In this study, we aim to identify which protein regions cause specific proteins to aggregate, which may lead them to be involved in mental illness. To do this, we are cloning fragments of the genes encoding these proteins, and then expressing protein fragments in human cell lines. These are subsequently analysed by immunofluorescent microscopy to determine the presence of protein aggregates in the cells. So far, we have found that an unstructured region in the centre of the protein DISC1 (Disrupted in Schizophrenia 1) forms the basis for its aggregation. DISC1 is a protein that takes part in scaffolding protein and regulates neurodevelopment. We are expanding our research to try and determine critical regions of other proteins of interest in mental illnesses. Further research on the biology of mental illnesses would potentially provide new means for their diagnosis, treatment and prognosis.

Mental illness ; protein aggregation ; proteostasis ; DISC1

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