阿玆海默症 (Alzheimer’s disease, AD)，又稱老人失智症，是一種漸進式的神經退化性疾病。主要的病理特徵有貝它糊蛋白斑塊的沉澱及神經纖維化的糾結。貝它糊蛋白中最主要的成分是Amyloid-b (Ab)，是由細胞膜上的Ab前趨蛋經由酵素白切割而產生的，具有40或42個胺基酸長的蛋白質。近年研究發現，腦中貝它糊蛋白的聚集可能是由於Ab不正常的代謝所造成。先前的實驗發現，血紅素會和Ab結合並且促使Ab寡聚體的形成。並且，血紅素和Ab共存於阿茲海默症患者腦中。然而，血紅素和Ab兩者之間作用的機制仍不清楚。因此，本實驗主要目的是要探討血紅素對於Ab的聚集、毒性及代謝所造成的影響。實驗發現，血紅素中heme的部分和Ab有很強的結合力，並且hemin對於Ab的聚集會隨著時間及劑量的增加而有增加的趨勢。而在Ab-hemin結合過程中，鐵離子扮演了一個必要的角色。Ab和hemin結合的位置可能位於第17-40個胺基酸的位置。實驗亦發現同樣含有heme的肌紅素以及細胞色素C也具有和Ab結合的能力。雖然hemin有促進Ab寡聚體形成的能力，但在長時間的反應中，hemin並不會改變Ab纖維化的過程。最後，hemin會改變Ab對於神經瘤母細胞SH-SY5Y的毒性並且也會改變Ab切割酶neprilysin對Ab的水解過程。

The pathological hallmarks of Alzheimer's disease (AD) include the deposition of amyloid plaques extracellularly and neurofibrillary tangles intracellularly. β-Amylold (A), the major composition of amyloid plaque, is a 40- or 42-amino-acid long peptide that is formed by the proteolytic cleavages of -amyloid precursor protein. Recent evidence indicates Aβ accumulation may be initiated due to its abnormal metabolism. Previously, hemoglobin (Hb) was identified as a potent A binding protein that was capable of promoting A aggregation. In addition, Hb was found to be co-localized with A in amyloid plaques and cerebral amyloid angiopathy, suggesting that Hb may be involved in A accumulation in AD brain. However, the molecular interaction between Hb and A remains unclear. The objective of this study is to explore the effects of Hb on A 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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