The main component of the amyloid plaque is insoluble Aβ1-42 (Aβ42), which adopts a structure rich in antiparallel β-pleated sheets. Recently, increasing awareness of Aβ intermediates as molten-globule states has paralleled insight into the biological activities of the Aβ conformer. The molten-globule state of Aβ42 displays a less ordered, metastable conformation that is stabilized by the formation of fibrils. The molten-globule state of the protein has many biological properties and understanding the mechanisms of its formation is an important step in devising a therapeutic strategy for Alzheimers disease. There have been many studies of the biological properties of Aβ42 such as self-aggregation, binding to other proteins such as apolipoprotein E, cytotoxicity for neuronal cells, vasoconstriction, oxidative activity with superoxide-mediated singlet-oxygen intermediate and proteolytic activity against casein. Recent studies demonstrated that α-1 anti-chymotrypsin, a member of the serine protease inhibitor (serpin) family is also involved in the amyloid plaque. In this review, we focused on the serine protease-like activity of Aβ42 for casein substrate and the effect of bio-essential metal ions for the activity and also suggest its inhibition with Aβ42 derivatives; Aβ15-22 (QKLVFFAE) which is a potential fragment to prevent Aβ self-aggregation. Consequently, we suggest that the short peptides of this kind may be of use in the therapy of Alzheimers disease.
Keywords: alzheimers disease, guanidine hydrochloride, molten-globule, ab peptides, serine protease-like activity, selfaggregation, metal ions, eight-residue derivatives
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