The Science

Gsalpha (Gsα) is part of the heterotrimeric G protein complex, a key coupling protein between cell-surface neurotransmitter receptors and intracellular signaling pathways. The alpha subunit of the stimulatory G protein (Gsa) activates the enzyme adenylyl cyclase which also synthesizes the second messenger, cyclic AMP (cAMP). Increased cAMP facilitates intracellular signaling pathways including neuronal activity and neurotransmitter function.

Pax’s founder, Mark M. Rasenick PhD, discovered that much of the Gsα normally moves freely in the membrane to activate adenylyl cyclase to produce cAMP. This supports proper neuronal activity/neurotransmitter function.

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In depressed subjects, Gsα sequesters in specialized regions of cell membranes, called lipid rafts, which restrict its signaling capability, weakening Gsα’s activation of adenylyl cyclase through neurotransmitters like serotonin and norepinephrine, and “depressing” neuronal cellular activity. When depression is treated effectively, Gsα moves out of lipid raft regions into the more fluid regions of the cell membrane. This normalizes the adenylyl cyclase/cAMP cascade and neuronal activity. Variations in lipid raft localization of Gsα in platelets correlate with the severity of depressive symptoms as well as the alleviation of those symptoms caused by effective therapy.

Pax’s proprietary product platform, MoodMark®, uses a blood draw and a simple biochemical assay to quantify circulating vs. sequestered levels of Gsα. This provides the first objective, quantitative biochemical “signature” of the existence and severity of depression. By retesting within a few days of starting therapy, MoodMark® might also provide a rapid, objective predictor of the treatment’s ultimate effectiveness in alleviating depression. 

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