Cell and Molecular Biology Graduate Group, The Combined Degree Program, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Hematol Oncol Clin North Am. 2010 Dec;24(6):1071-88. doi: 10.1016/j.hoc.2010.08.013.
Erythrocytes must regulate hemoglobin synthesis to limit the toxicities of unstable free globin chain subunits. This regulation is particularly relevant in β-thalassemia, in which β-globin deficiency causes accumulation of free α-globin, which forms intracellular precipitates that destroy erythroid precursors. Experimental evidence accumulated over more than 40 years indicates that erythroid cells can neutralize moderate amounts of free α-globin through generalized protein quality control mechanisms, including molecular chaperones, the ubiquitin-proteasome system, and autophagy. In many ways, β-thalassemia resembles protein aggregation disorders of the nervous system, liver, and other tissues, which occur when levels of unstable proteins overwhelm cellular compensatory mechanisms. Information gained from studies of nonerythroid protein aggregation disorders may be exploited to further understand and perhaps treat β-thalassemia.
红细胞必须调节血红蛋白的合成以限制不稳定游离珠蛋白链亚基的毒性。这种调节在β-地中海贫血中尤为重要，因为β-珠蛋白的缺乏导致游离α-珠蛋白的积累，游离α-珠蛋白形成破坏红系前体细胞的细胞内沉淀物。40 多年来积累的实验证据表明，红细胞可以通过包括分子伴侣、泛素-蛋白酶体系统和自噬在内的一般蛋白质质量控制机制来中和适量的游离α-珠蛋白。在许多方面，β-地中海贫血类似于神经系统、肝脏和其他组织的蛋白质聚集紊乱，当不稳定蛋白质的水平超过细胞代偿机制时，就会发生这种疾病。从非红细胞蛋白聚集紊乱研究中获得的信息可能被利用来进一步理解β-地中海贫血，甚至可能用于治疗。
