2016年7月10日日曜日

Melatonin from pineal gland must be a PAK1-blocker.

Melatonin, an anti-melanogenic, anti-ageing and anti-cancer hormone from pineal gland in brain, is a Trp derivative which is biosynthesized from Serotonin.  Treatment of ageing mice, rats or fruit flies (Drosophila) with Melatonin extends their healthy lifespan by 20% (1, 2). 



Recently it was found that melatonin activates the anti-oncogenic/anti-ageing kinase AMPK (3).  Furthermore, melatonin blocks the oncogenic kinase ERK (4).  ERK is down-stream of the oncogenic/ageing/melanogenic kinase PAK1, and almost all herbal AMPK activators such as propolis block PAK1. More interestingly, melatonin activates HSP (heat shock protein) genes which are normally suppressed by PAK1, strongly suggesting that melatonin also blocks PAK1.



Thus, we are currently confirming this notion, and planning to develop a much more potent (both highly cell-permeable and water-soluble) derivative of melatonin for clinical use.



In US, melatonin has been widely used as an inexpensive and safe "sleeping pill" by those who are suffering from sleeping disorders such as jet-lag.




References: 

1.Maestroni GJ, Conti A, Pierpaoli W.
Pineal melatonin, its fundamental immunoregulatory role in aging and cancer.
Ann N Y Acad Sci. 1988; 521: 140-8.



2. Anisimov VN, Mylnikov SV, Khavinson VK.
Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats. Mech Ageing Dev. 1998; 103: 123-32.


3. Rui BB1, Chen H2, Jang L1, Li Z1, Yang JM3, Xu WP4, Wei W5.
Melatonin Upregulates the Activity of AMPK and Attenuates Lipid Accumulation in Alcohol-induced Rats. Alcohol Alcohol. 2016; 51(1):11-9.  


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