The prevalence of degenerative neuro-diseases such as Alzheimer’s disease has increased with an increase in the life expectancy especially as seen in developed countries. According to the Amyloid Hypothesis, β-secretase leads to the onset of Alzheimer's disease though the generation of amyloid-β by proteolysis of amyloid precursor protein. Amyloid-β aggregates to form oligomers that build up to form plaques. Olive flounder (Paralichthys olivaceus) is high in protein content, with a higher protein content in skin (27.65%) compared to muscle (19.65%) according to proximate analysis results. Enzyme hydrolysates were prepared from skin and muscle using several enzymes. The neutrase skin hydrolysate showed the highest β-secretase inhibitory activity IC₅₀ 0.61 mg/mL. Purification steps were performed using ion exchange chromatography on QMA and CM-cellulose columns and SPE C18 column to produce an active fraction QMA-F1 with an IC₅₀ value of 32.80 µg/mL. QMA-F1 was non-cytotoxic to SH-SY5Y cells, reduced BACE1 overexpression and attenuated amyloidogenesis. This suggests that the active β-secretase inhibitory peptides from olive flounder skin hydrolysates can be utilized as an ingredient in development of new pharmaceutical and nutraceutical therapeutic agents for Alzheimer’s Disease.

Graphic Abstract

中文翻译：

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橄榄比目鱼（Paralichthys olivaceus）皮肤水解物的肽级分通过抑制BACE1表达抑制SH-SY5Y细胞中淀粉样β的生成。

退化性神经疾病（例如阿尔茨海默氏病）的患病率随着预期寿命的增加而增加，特别是在发达国家。根据淀粉样蛋白假说，尽管β-分泌酶通过淀粉样蛋白前体蛋白的蛋白水解产生淀粉样蛋白-β，但却导致阿尔茨海默氏病的发作。淀粉样蛋白-β聚集形成寡聚体，这些寡聚体积聚形成斑块。根据最近的分析结果，比目鱼（Paralichthys olivaceus）的蛋白质含量高，皮肤中的蛋白质含量（27.65％）比肌肉（19.65％）高。使用几种酶从皮肤和肌肉制备酶水解物。中性皮肤水解产物显示出最高的β-分泌酶抑制活性IC ₅₀0.61 mg / mL。使用离子交换色谱法在QMA和CM-纤维素柱以及SPE C18柱上进行纯化步骤，以生产具有IC ₅₀值为32.80 µg / mL的活性级分QMA-F1 。QMA-F1对SH-SY5Y细胞无细胞毒性，可减少BACE1的过表达并减弱淀粉样蛋白的生成。这表明来自橄榄比目鱼皮肤水解产物的活性β-分泌酶抑制肽可用作开发用于阿尔茨海默氏病的新型药物和营养治疗剂的成分。

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