Abstract
Abstract Alzheimer's disease ( AD ) is one of the most fatal neurodegenerative disease .The major pathogenesis of Alzheimer's disease ( AD ) is neurofibrillary tangles and enile plaques, and the aggregation of the A 40 plays a crucial role in the pathogenesis of the senile plaques of Alzheimer's disease (AD) . Although the amyloid -protein has been studied extensively, the mechanisms of A aggregation in brain remain unclear . In this study, we investigate the influence of the collagen related peptides on A aggregation. Here we chose the most important region of amyloid -protein responsible for aggregation, residues 16-22 (KLVFFAE), as our study model . We incorporated the collagen sequence (POG)n into Aβ(16-22) and synthesized eight peptides: WT-A(16-22), A(16-22)-(POG)6, A(16-22)-(POG)7, A(16-22)-(POG)10, (POG)7-A(16-22) and (POG)10-A(16-22).Two collagen peptides (POG)7 and (POG)10 were synthesized as the control peptides for comparison.We used fluorescence spectroscopy, TEM, CD, FT-IR and DLS to study whether the collagen sequence can inhibit A aggregation . CD measurements indicate that the Aβ(16-22) sequence at the N-terminus of (POG)n does not stabilize the triple-helical structure of collagen and such peptides have a weaker thermal stability than (POG)n .In contrast,when the Aβ(16-22) sequence is attached to the C-terminus of (POG)n, it can stablize the triple-helical structure of collagen. From aggregation studies, we found that the amyloid aggregation did not occur when (POG)7 was incorporated into A(16-22) but the aggregation was enhanced when (POG)10 incorporated into A(16-22).The mixing experiments indicate that (POG)7A cannot inhibit the aggregation of WT-A(16-22) while A(POG)6 and A(POG)7 can.The inhibition effect may not be due to the triple-helical structure of collagen but the PPⅡ structure.