engleski

Co-aggregation of proteins involved in mental illness

Chronic mental disorders (CMD), including bipolar disorder, major depression disorder, and schizophrenia, are complex conditions characterized by both genetic and non-genetic elements. However, their underlying biological causes remain relatively unknown. Determining a specific biological cause for any of these illnesses may provide us with a drug target whose design would be the next step in defeating these illnesses. Over the past several years, a number of studies proposed the presence of disturbed proteostasis as a possible pathological cause of non-genetic cases of chronic brain disorders. The idea of aggregation of one or multiple proteins (co-aggregation) derived from research that established that disturbance of proteostasis in the brain could be one of the key features for developing such disorders. Providing evidence of co-aggregation of certain proteins could give us more insight into understanding the biological causes of specific brain disorders. We are investigating the presence of co-aggregates through expressing proteins of interest firstly in neuroblastoma cell line, SHSY5Y, and, if proteins are proven to co-aggregate, testing brain tissue samples for expression of these aggregated proteins. Previous studies characterized a number of proteins that are known to misassemble in CMD, which are CRMP1, dysbindin-1, DISC1, NPAS3, and TRIOBP-1. We have already seen some proteins co- aggregate, such as DISC1 with CRMP1 and dysbindin- 1, while others do not such as TRIOBP-1 with DISC1 and CRMP1. We are now expanding these studies to investigate the co-aggregation between other proteins found in CMD and to look at whether their aggregation affects other known interaction partners. We are hoping that the results of our research will contribute to understanding the biological causes of CMD and possibly lead to subsequent research on designing drugs that could effectively treat those illnesses.

mental disorders ; protein aggregation ; proteostasis ; schizophrenia

nije evidentirano