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by | Mar 16, 2018 | Hosta

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Smoothened agonist (SAG) was one of the first small-molecule agonists developed for the protein Smoothened,[1] a key part of the hedgehog signaling pathway, which is involved in brain development as well as having a number of other functions in the body.

Smoothened agonist has been shown to aid proliferation and survival of developing neurons,[2] and prevent drug-induced brain injury.[3] When injected into the cerebellum of newborn mice with an induced Down syndrome-like condition, Smoothened agonist was able to stimulate normal cerebellum development, resulting in significant behavioural improvement once the mice had grown to adulthood.[4]

Smoothened Agonist was capable of inducing androgen production in both prostate and bone stromal cells that was significantly greater than even similarly treated prostate cancer cells.[5]

The substance has been used as part of a chemical cocktail to turn old and senescent human cells back into young ones (as measured by transcriptomic age), without turning them all the way back into undifferentiated stem cells.[6]

References

  1. ^ Lewis C, Krieg PA (August 2013). "Reagents for developmental regulation of Hedgehog signaling". Methods. 66 (3): 390–397. doi:10.1016/j.ymeth.2013.08.022. PMID 23981360.
  2. ^ Bragina O, Sergejeva S, Serg M, Zarkovsky T, Maloverjan A, Kogerman P, Zarkovsky A (September 2010). "Smoothened agonist augments proliferation and survival of neural cells". Neurosci. Lett. 482 (2): 81–5. doi:10.1016/j.neulet.2010.06.068. PMID 20600593. S2CID 24186568.
  3. ^ Heine VM, Griveau A, Chapin C, Ballard PL, Chen JK, Rowitch DH (October 2011). "A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury". Sci Transl Med. 3 (105): 105ra104. doi:10.1126/scitranslmed.3002731. PMC 3694585. PMID 22013124.
  4. ^ Das I, Park JM, Shin JH, Jeon SK, Lorenzi H, Linden DJ, Worley PF, Reeves RH (September 2013). "Hedgehog agonist therapy corrects structural and cognitive deficits in a down syndrome mouse model". Sci Transl Med. 5 (201): 201ra120. doi:10.1126/scitranslmed.3005983. PMC 4006719. PMID 24005160.
  5. ^ Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, Pham S, Buttyan R (2016). "Paracrine Sonic Hedgehog Signaling Contributes Significantly to Acquired Steroidogenesis in the Prostate Tumor Microenvironment". International Journal of Cancer. 140 (2): 358–369. doi:10.1002/ijc.30450. PMID 27672740. S2CID 2354209.
  6. ^ Yang, Jae-Hyun; Petty, Christopher A.; Dixon-McDougall, Thomas; Lopez, Maria Vina; Tyshkovskiy, Alexander; Maybury-Lewis, Sun; Tian, Xiao; Ibrahim, Nabilah; Chen, Zhili; Griffin, Patrick T.; Arnold, Matthew; Li, Jien; Martinez, Oswaldo A.; Behn, Alexander; Rogers-Hammond, Ryan (2023-07-12). "Chemically induced reprogramming to reverse cellular aging". Aging. 15 (13): 5966–5989. doi:10.18632/aging.204896. ISSN 1945-4589. PMC 10373966. PMID 37437248.
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