| Summary: | 碩士 === 國立成功大學 === 細胞生物及解剖學研究所 === 94 === The pathological hallmarks of Alzheimer's disease (AD) include the deposition of amyloid plaques extracellularly and neurofibrillary tangles intracellularly. β-Amylold (Ab), the major composition of amyloid plaque, is a 40- or 42-amino-acid long peptide that is formed by the proteolytic cleavages of b-amyloid precursor protein. Recent evidence indicates Aβ accumulation may be initiated due to its abnormal metabolism. Previously, hemoglobin (Hb) was identified as a potent Ab binding protein that was capable of promoting Ab aggregation. In addition, Hb was found to be co-localized with Ab in amyloid plaques and cerebral amyloid angiopathy, suggesting that Hb may be involved in Ab accumulation in AD brain. However, the molecular interaction between Hb and Ab remains unclear. The objective of this study is to explore the effects of Hb on Ab aggregation, toxicity and enzymatic degradation. Our results showed that, heme bound avidly to Ab and affected Ab aggregation in time- and dose-dependent manners. Besides, Fe2+ ion participated in the heme-Ab complex formation. Such heme-Ab interaction was effectively disrupted by the C-terminal hydrophobic domain Ab17-40. Other heme-containing proteins, such as myoglobin and cytochrome C, also bound to Ab. However, heme did not alter Ab fibrillogenic ability. Importantly, heme altered both the Ab-elicited neurotoxicity in SH-SY5Y neuroblastoma cells and the Ab metabolism on neprilysin-elicited proteolytic degradation.
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