PE 22-28

What is PE-22-28?

PE-22-28 is a synthetic derivative of the naturally occurring peptide spadin. Spadin is a secreted peptide derived from sortilin. It is an antagonist of the TREK-1 (TWIK-related-potassium channel) receptor, a two-pore potassium channel identified as a potential target in the treatment of depression and as a possible neurogenic regulator. Early studies in mice have shown that a deletion of the TREK-1 receptor makes them resistant to depression. Similarly, treatment with sortilin leads to resistance to depression boosts the growth of both neurons and the synaptic interconnections between neurons[1].

Interestingly, shortened analogs of spadin actually show better TREK-1 inhibition than spadin itself. PE-22-28 is the representative peptide for this group of synthetic spadin analogs. PE-22-28 has been shown to be more stable and have improved antidepressant activity and neurogenic properties over the naturally occurring spadin.

It is important to note that one of the long-term consequences of taking anti-depressant medications (e.g. SSRIs) is neurogenesis. In fact, the growth of new neurons is considered to be one indication that depression is being adequately treated and that antidepressants are working. PE-22-28 has been shown to induce neurogenesis after just 4 days, which is substantially faster than any known antidepressant. This also suggests that PE-22-28 might be useful in other applications such as learning, stroke recovery, and perhaps even the battle against neurodegenerative diseases[2].

TREK-1, which is primarily found in the brain, is also found in the heart, smooth muscle cells, lung tissue, the prostate, and in specific areas of the pancreas. Though it has been primarily studied as a target for antidepressant activity, TREK-1 plays important roles in pain perception, anesthesia, and neuroprotection. These properties have made TREK-1 a major research target in academia and industry.