Aksenov M Y, Aksenova M V, Carney J M, Butterfield D A
Department of Pharmacology, University of Kentucky, Lexington 40536, USA. myakse
Neurosci Lett. 1996 Oct 18;217(2-3):117-20.
alpha 1-Antichymotrypsin (ACT) is intimately associated with senile plaques in the Alzheimer's diseased (AD) brain. It was reported that ACT can promote the polimerization of A beta (1-42) into amyloid filaments. It was suggested that neurotoxic amyloid deposits arise when beta-peptide is induced to form fibrils by ACT or other amyloid-promoting factors (pathological chaperones) expressed in AD brain. However, it was reported recently that ACT can inhibit fibrillization of A beta (1-40) and disaggregate pre-formed beta-amyloid fibrils of this synthetic A beta peptide. Our previous study [Aksenova et al., Neurosci. Lett., 411 (1996) 43-48] confirmed that ACT is able to inhibit A beta (1-40) aggregation into fibrils, but it was shown that at the same time ACT does not change the peptide cytotoxicity. In this report we have observed that interaction of ACT with A beta (1-42), unlike that for ACT-A beta (1-40) interaction, does not prevent the formation of insoluble A beta (1-42) aggregates, but completely blocks the peptide's toxicity in rat hippocampal cell cultures. These results are discussed in terms of the potential double role of peptide-protein interactions on A beta aggregation and neurotoxicity.
α1-抗糜蛋白酶（ACT）与阿尔茨海默病（AD）患者大脑中的老年斑密切相关。据报道，ACT可促进Aβ（1-42）聚合成淀粉样纤维。有人提出，当β-肽被AD大脑中表达的ACT或其他淀粉样蛋白促进因子（病理性伴侣蛋白）诱导形成纤维时，就会产生神经毒性淀粉样沉积物。然而，最近有报道称，ACT可抑制Aβ（1-40）的纤维化，并使这种合成Aβ肽预先形成的β-淀粉样纤维解聚。我们之前的研究[Aksenova等人，《神经科学快报》，411（1996）43-48]证实，ACT能够抑制Aβ（1-40）聚合成纤维，但同时也表明ACT不会改变该肽的细胞毒性。在本报告中，我们观察到，与ACT-Aβ（1-40）相互作用不同，ACT与Aβ（1-42）的相互作用不会阻止不溶性Aβ（1-42）聚集体的形成，但会完全阻断该肽在大鼠海马细胞培养物中的毒性。我们将根据肽-蛋白质相互作用对Aβ聚集和神经毒性的潜在双重作用来讨论这些结果。
