Schizophrenia is a serious mental illness that affects 1% of the population, costing Canadians over 2 billion dollars a year. Antipsychotic medications are the most commonly prescribed treatments for schizophrenia, however they fail to improve many cognitive and behavioral abnormalities and can cause serious side effects, driving researchers to try and find alternate treatments.
There is a clear genetic component to schizophrenia and researchers believe that identifying genetic variants or mutations in patients with schizophrenia will provide clues about underlying causes of this disease as well as provide targets for the development of therapeutics. It is unlikely that schizophrenia is caused by mutations in one gene, but rather by mutations in combinations of different genes that lead to impairments in brain development and function. This is likely compounded when mutations occur in gene products found in the same signaling pathway or that mediate the same biological processes.
Dr. Shernaz Bamji and her lab hypothesize that disruptions in a chemical process called ‘palmitoylation’ may play a central role in the development of schizophrenia and that this can be caused by mutations in both the enzymes that palmitoylate proteins as well as the proteins that are palmitoylated. Specifically, they hypothesize that the DHHC5 enzyme is a master regulator of a key signaling “hub” that is disrupted in patients with this disease.
Using neurons grown in culture as well as transgenic mouse models, they will determine whether DHHC5 malfunction leads to aberrant brain development and behaviors associated with schizophrenia, and whether targeting this pathway is a viable therapeutic option to normalize brain health.