Novel brain protein can treat major depressive disorder
Recent research has identified that a novel protein player in molecular mechanism of depression operating in brain cells can form the substrate for treating the malady. This protein with a defined role in growth and development of brain cells can interact with antidepressants during the cure process.
Major depressive disorder is described as “the most common and debilitating neurobiological illnesses”. The biology of this form of depression is largely unknown. It occurs due to monetary burden ($100 billion annually) and is characterized by lifetime prevalence. This paper is a report of mechanism functioning in cells leading to depression. Research leading to these findings was conducted by Ronald S Duman and his colleagues at Yale University and this work is published this year in Letter’s section, October edition of Nature medicine.
In this study, mRNA levels were used as a measure to compare differences in gene activity in normal and diseased tissue. Brain samples from 21 depressed people formed the experimental group. A similar set of samples from 18 normal people was collected post mortem for control tests. mRNA levels of a particular gene, mkp-1, doubled in brains of depressed patients. The protein MKP-1 is a negative regulator of MAP Kinase cascade in brain cells. By dephosphorylating threonine and tyrosine amino acids this protein prevents the signal transduction cascade responsible for neuronal plasticity, function and survival. The difference in expression of MKP-1 was most significant among all the observed variations.
The research group also established in vivo evidence for association between MKP-1 levels and depression using mouse models. They over-expressed MKP-1 in brains of healthy rats and noted signs of depression. Even more significant was the disappearance of depression in these rats when treated with antidepressants. The scientists conclude that MKP-1 is a novel target for antidepressants. Further they hypothesize that MKP-1 can be used as a target for therapeutic drug development in depression.