Christie G, Markwell R E, Gray C W, Smith L, Godfrey F, Mansfield F, Wadsworth H, King R, McLaughlin M, Cooper D G, Ward R V, Howlett D R, Hartmann T, Lichtenthaler S F, Beyreuther K, Underwood J, Gribble S K, Cappai R, Masters C L, Tamaoka A, Gardner R L, Rivett A J, Karran E H, Allsop D
SmithKline Beecham Pharmaceuticals, Harlow, Essex, England, UK.
J Neurochem. 1999 Jul;73(1):195-204. doi: 10.1046/j.1471-4159.1999.0730195.x.
Peptide aldehyde inhibitors of the chymotrypsin-like activity of the proteasome (CLIP) such as N-acetyl-Leu-Leu-Nle-H (or ALLN) have been shown previously to inhibit the secretion of beta-amyloid peptide (A beta) from cells. To evaluate more fully the role of the proteasome in this process, we have tested the effects on A beta formation of a much wider range of peptide-based inhibitors of CLIP than published previously. The inhibitors tested included several peptide boronates, some of which proved to be the most potent peptide-based inhibitors of beta-amyloid production reported so far. We found that the ability of the peptide aldehyde and boronate inhibitors to suppress A beta formation from cells correlated extremely well with their potency as CLIP inhibitors. Thus, we conclude that the proteasome may be involved either directly or indirectly in A beta formation.
蛋白酶体类胰凝乳蛋白酶样活性（CLIP）的肽醛抑制剂，如N-乙酰-亮氨酰-亮氨酰-正亮氨酸-H（或ALLN），先前已被证明可抑制细胞中β-淀粉样肽（Aβ）的分泌。为了更全面地评估蛋白酶体在此过程中的作用，我们测试了比先前报道的范围更广的基于肽的CLIP抑制剂对Aβ形成的影响。所测试的抑制剂包括几种肽硼酸酯，其中一些被证明是迄今为止报道的最有效的基于肽的β-淀粉样蛋白生成抑制剂。我们发现，肽醛和硼酸酯抑制剂抑制细胞中Aβ形成的能力与其作为CLIP抑制剂的效力密切相关。因此，我们得出结论，蛋白酶体可能直接或间接参与Aβ的形成。
