User:Katimohe/protein P11 project proposal

Pathology

Protein p11 has been intimately linked to mood disorders due to its role in serotonin systems via its interactions with serotonin 5-HT receptors. Though serotonin affects diverse systems (including the cardiovascular, renal, immune, and gastrointestinal systems), the neurotransmitter’s close, though enigmatic relationship with mood-regulation is where current research is focused.

Depression is a widespread, debilitating disease affecting persons of all ages and backgrounds and is characterized by a plethora of emotional and physiological symptoms including feelings of sadness, hopelessness, pessimism, guilt, a general loss of interest in life, and a sense of reduced emotional well-being or low energy. Unfortunately, much of the underlying pathophysiology of clinical depression and other related mood-disorders including anxiety, Bipolar Disorder, ADD, ADHD, and Schizophrenia remain shrouded in mystery. Understanding the mechanism by which Protein p11 regulates serotonin sheds some light on this mystery, as research has shown that low levels of Protein p11 directly correlates with depression in humans and mice.

Recent studies have seen that the levels of p11 rose in depressed mice at the same rate that the drugs affected their behavioral changes and that knockout experiments in which the gene coding for Protein p11 was deleted from the mouse genome caused them to show signs of depression. In addition, post-mortem comparisons of brain tissues showed much lower levels of p11 in depressed compared to control subjects.

Most of the current drugs and treatments for depression and anxiety increase levels of serotonin transmission among neurons. Selective Serotonin Reuptake Inhibitors (SSRIs), a very successful class of drugs, are known to increase the amount of serotonin available to brain cells quite rapidly. Despite this, their therapeutic effects take a period of several weeks or months. Recent studies have shown that Protein p11 increases the concentration of the serotonin 5-HT receptors at neuronal synapses, thereby rendering serotonin signaling much more efficient. These findings suggest that although the serotonin levels are immediately introduced into one’s system with the medication, the period of time which it takes the medicine to alleviate the patient’s depression most likely relies on some other involved regulatory protein. Thus, Protein p11’s interaction with serotonin 5-HT receptors and the increasing evidence of the protein’s correlation to mood disorders has identified this protein as a target for research in the development of future antidepressants.