Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
Department of Haematology, Faculty of Medical Laboratory Sciences, Al-Neelain University, Khartoum, Sudan.
Int J Hematol. 2020 Mar;111(3):352-359. doi: 10.1007/s12185-019-02806-8. Epub 2020 Jan 1.
Hemoglobin (Hb) is an iron-containing metalloprotein that transports oxygen molecules from the lungs to the rest of the human body. Among the different variants of Hb, HbA1 is the most common and is composed of two alpha (αHb) and two beta globin chains (βHb) constructing a heterotetrameric protein complex (αβ). Due to the higher number of AHSP genes, there is a tendency to produce approximately twice as much of α subunit as β subunit. Therefore, there is a chance of presenting excess α subunit leftover in human blood plasma; excess subunits subsequently bind with each other and aggregates β-thalassemia occurs due to lack of or reduced numbers of βHb subunit. Alpha-hemoglobin-stabilizing protein (AHSP) is a scavenger protein which acts as a molecular chaperon by reversibly binding with free αHb forming a complex (AHSP-αHb) that prevents aggregation and precipitation preventing deleterious effects towards developing serious human diseases including β-thalassemia. Clinical severity worsens if mutations in AHSP gene co-occur in patients with β-thalassemia. Considering the mechanism of action of AHSP and its contribution to ameliorating β-thalassemia severity, it could potentially be used as a modulatory agent in the treatment of β-thalassemia.
血红蛋白（Hb）是一种含铁的金属蛋白，它将氧分子从肺部输送到人体的其他部位。在 Hb 的不同变体中，HbA1 最为常见，由两条α（αHb）和两条β珠蛋白链（βHb）组成，构成异四聚体蛋白复合物（αβ）。由于 AHSP 基因数量较多，产生的α亚基数量比β亚基多约两倍。因此，人血浆中可能会出现多余的α亚基；多余的亚基随后相互结合，由于βHb 亚基数量减少或缺失，β-地中海贫血发生。α-血红蛋白稳定剂蛋白（AHSP）是一种清除蛋白，它通过可逆地与游离的αHb 结合形成复合物（AHSP-αHb）来充当分子伴侣，从而防止聚集和沉淀，防止对发育严重人类疾病（包括β-地中海贫血）产生有害影响。如果β-地中海贫血患者的 AHSP 基因发生突变，临床严重程度会恶化。考虑到 AHSP 的作用机制及其对改善β-地中海贫血严重程度的贡献，它有可能被用作β-地中海贫血治疗的调节剂。
