Image: Neurons derived from skin cells of patients with schizophrenia express high levels of a protein linked to Alzheimer’s / Photo: Courtesy of Icahn School of Medicine at Mt. Sinai
According to a new study, a protein previously associated with Alzheimer’s disease may play a role in genetic predisposition to schizophrenia. Therefore, a drug that targets that protein may also help to treat schizophrenia.
This protein is called STriatal-Enriched Protein Tyrosine Phosphatase, or STEP, which plays a role in healthy synaptic function. Several studies have found that STEP levels in the brains of animal models and humans are disrupted in several diseases. The first disease linked with increased STEP expression is Alzheimer’s disease. Further studies also linked it to fragile X syndrome, schizophrenia, and Parkinson’s disease. The evidence shows that increase levels of this protein contribute to cognitive deficits by disrupting synaptic function.
In a previous research, the group of Yale researchers showed that an experimental STEP inhibitor restored cognitive deficits in mouse models of Alzheimer’s disease. In new study a team lead by Paul Lombroso, professor and researchers at Yale University, showed that using a STEP inhibitor or genetically eliminating STEP in mouse models with behavioural symptoms related to schizophrenia improves their cognitive deficits.
Furthermore, a second team led by Kristen Brennand, researcher at the Icahn School of Medicine at Mount Sinai, detected increase levels of STEP in pluripotent human stem cells induced from adult skin cells taken from schizophrenia patients. When a STEP inhibitor was used in those cells, the biochemical and electrophysiological deficits found in them were corrected.
The experimental STEP inhibitor previously used resulted difficult to develop for clinical use, therefore the researchers are hoping that new STEP inhibitors, developed by professors Eric Ellman in chemistry and Angus Nairn in psychiatry, can be more practical for therapy.
“These findings suggest that a STEP inhibitor, when discovered, may be the basis of a new drug that can treat a number of neuropsychiatric disorders,” Lombroso said.
The study, published in the journal Molecular Psychiatry, was funded by the National Institutes of Health, the New York Stem Cell Foundation, and the Brain and Behavior Research Foundation.
Source: Yale News
