Gamma secretase inhibitor

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γ-secretase inhibitors are potential drugs that inhibit the enzyme γ-secretase . As inhibitors of this enzyme, they suppress the formation of the β-amyloid from the amyloid precursor protein, which occurs in deposits ( plaques ) in the brains of Alzheimer's patients . In addition, they inhibit the function of γ-secretase in the activation of Notch , a receptor that is involved in the control of cell processes. Possible therapeutic areas of application for γ-secretase inhibitors are the treatment of Alzheimer's disease and cancer therapy . Numerous side effects, which particularly affect the gastrointestinal tract and can be attributed to an inhibition of Notch, can, however, prevent future therapeutic use. Examples of γ-secretase inhibitors are Semagacestat , DAPT , LY 450139 and MK-0752 . Some established drugs from the family of nonsteroidal anti-inflammatory drugs , such as R - flurbiprofen and sulindac , inhibit γ-secretase as allosteric modulators .

Individual evidence

  1. ↑ a b Imbimbo BP: Therapeutic potential of gamma-secretase inhibitors and modulators . In: Curr Top Med Chem . 8, No. 1, 2008, pp. 54-61. PMID 18220933 .
  2. ↑ Shih IeM, Wang TL: Notch signaling, gamma-secretase inhibitors, and cancer therapy . In: Cancer Res . 67, No. 5, March 2007, pp. 1879-82. doi : 10.1158 / 0008-5472.CAN-06-3958 . PMID 17332312 .
  3. ↑ Beher D, Clarke EE, Wrigley JD, et al. : Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site. Evidence for an allosteric mechanism . In: J Biol Chem . 279, No. 42, October 2004, pp. 43419-26. doi : 10.1074 / jbc.M404937200 . PMID 15304503 .