Substrate-targeting γ-secretase modulators

lzheimer's disease: γ-secretase modulators target Aβ42 One promising approach to Alzheimer's disease treatment involves the use of drugs to reduce the rate of deposition of Aβ42, the 42-residue form of amyloid-β peptide, by curbing its generation. Certain non-steroidal anti-inflammatory drugs known as γ-secretase modulators or GSMs, including ibuprofen and sulindac, have this capacity but how they work is unclear. Now their target has been identified as a site on Aβ42 itself — rather than the presenilins or a core β-secretase component. By binding to Aβ42 these drugs inhibit not only its rate of production but also its aggregation.