An enzyme known as MKP-1 is linked to depression and could potentially be a new target for therapy of the disorder reports an article online this week in Nature Medicine.
The prevalence and economic burden associated with depression make it one of the most debilitating neurobiological illnesses. Despite this, the cellular and molecular mechanisms underlying the pathophysiology of depression are not entirely known. Ronald Duman and his colleagues applied genomic techniques to human brain tissue from people with depression and found increased expression of MKP-1. MKP-1 is a member of a family of proteins that remove phosphate groups from proteins and serves as a key negative regulator of the mitogen-activated protein kinase (MAPK) cascade — a major signaling pathway involved in neuronal function.
The authors tested the role of MKP-1 in rats and mice and found that increased MKP-1 expression caused depressive behaviours. Conversely, treatment with antidepressant normalized MKP-1 expression and behaviour, and mice lacking MKP-1 were resilient to stress-induced depressive pathology. This therefore underscores the potential relevance of this molecule to the pathophysiology of depression.