Pathways of p38, GSK3b, and Their Extensions to Mental Health

Nearly one in five adults in the United States experience mental illness during a year (NAMI). Neurobiological correlates of these diseases may provide treatment options if they are better understood. Research has provided evidence supporting p38’s role in many mental health disorders. P38 mitogen-activated protein kinases appear frequently in literature regarding cellular threats, such as UV irradiation, and subsequently serves various functions including cellular death. With respect to neurological and psychiatric disease, many of the observed effects are related to structures or substrates that are regulated, at least in part, by p38 or its downstream targets. The goal of this review is to examine the role of p38 in neural function and observable behavior as well as to review recent research suggesting a novel pathway through which p38 may act in response to DNA damage induced by psychological stress. This review will look through literature detailing p38’s pathway and its relation to the novel GSK3 serine site and DNA damage to make a case for these kinases’ activity as the underlying mechanism in many mental illnesses