The Antidepressant Peptide: PE-22-28 - Quick Telecast The Antidepressant Peptide: PE-22-28 - Quick Telecast The Antidepressant Peptide: PE-22-28 - Quick Telecast
Antidepressant Peptide

The Antidepressant Peptide: PE-22-28

Due to the seemingly random circumstances surrounding the discovery of PE-22-28, we will first discuss two precursor compounds. TWIK-related potassium channel-1 (TREK-1) was identified as a possible therapeutic target for treating depression in 2006:

 

The serotonin (5-hydroxytryptamine) receptor-like kinase 1 protein (TREK-1) is a background kinase K+ channel controlled by several neurotransmitters.

 

Mice with its gene deletion (Kcnk2, also known as TREK-1) showed improved 5-HT neurotransmission, resistance to depression across five models, and much lower corticosterone rise in response to stress. Mice lacking the TREK-1 gene (Kcnk2-/-) exhibited responses to traditional antidepressants that were consistent with those in other animals.

 

This has given researchers a new line of inquiry to pursue; by blocking TREK-1 with a potent antagonist, they may be able to treat depression. Particularly intriguing was the finding that TREK-1 is involved in strokes in a kind of sadness known as “Post-stroke depression” (PSD). As a result, French researchers found that a protein called Sortilin controlled TREK-1 activity.

 

Sortilin (also known as NTSR3 or neurotensin receptor-3) is a type-1 membrane protein that is 95-100 kDa in size and is made up of a lengthy luminal domain, a single transmembrane segment, and a short C-terminal cytoplasmic tail.

 

High levels of NTSR3/Sortilin and TREK-1 expression have been found in the rat prefrontal cortex, cingulate gyrus, amygdala, hippocampus, nucleus accumbens, dorsal raphe, and hypothalamus, all of which have a role in the pathophysiology of depression. As it turns out, the TREK-1 blockage was caused by a 44-amino-acid propeptide (PE) released into the circulation by this membrane protein.

 

The affinity with which propeptide binds to the functional receptor (Kd5 nM) is relatively strong. According to structure-function analyses, the peptide Gln1-Arg28 has the same binding activity as the full propeptide Gln1-Arg44, but the peptide Gln1-Arg16 has a very weak affinity.

 

Consequently, in 2010, Spadin (PE 12-28) was born. As a result, researchers created the peptide Spadin by preserving the sequence 17-28 and appending the sequence 12-16 (APLRP) to keep conformational stress in place. The effects of this partial propeptide (Ala12-Arg28) on regulating TREK-1 channels and their efficacy as an antidepressant medication were investigated using five different animal models of depression.

 

Spadin was shown to provide strong antidepressant effects in only 4 days (in contrast to fluoxetine, a standard medication that takes weeks to show its effects) with no adverse reactions. Six hours after injection, the anti-AD effects of Spadin were no longer present in vivo experiments. Researchers then looked for and found counterparts with the same characteristics but were more powerful and had better bioavailability in living organisms.

 

So, even though Spadin was far more effective at inhibiting TREK-1 than the original PE or fluoxetine, it was still not a realistic therapeutic target. The 7-amino acid peptide PE-22-28, also known as Mini-Spadin [Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR)], was discovered and synthesized in 2017 after researchers looked at shorter Spadin analogs.

 

Using the patch-clamp approach in vitro on hTREK-1/HEK cells, researchers found that PE 22-28 exhibited higher selectivity and affinity for the TREK-1 channel than spadin (IC50 = 0.12 nM vs. 40-60 nM for spadin).

 

Studies show that PE-22-28 is a natural and fast-acting therapeutic peptide that may cure depression better than existing TREK-1 blocking antidepressants like Cilatopram and Paroxetine. Its stability lasts for a total of 23 hours without degradation.

 

If this describes what you’re looking for, BiotechPeptides.com is the manufacturer for you.

 


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