Activation of pyruvate kinase as therapeutic option for rare hemolytic anemias: Shedding new light on an old enzyme

IF 6.9 2区 医学 Q1 HEMATOLOGY
Myrthe J. van Dijk , Jonathan R.A. de Wilde , Marije Bartels , Kevin H.M. Kuo , Andreas Glenthøj , Minke A.E. Rab , Eduard J. van Beers , Richard van Wijk
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引用次数: 1

Abstract

Novel developments in therapies for various hereditary hemolytic anemias reflect the pivotal role of pyruvate kinase (PK), a key enzyme of glycolysis, in red blood cell (RBC) health. Without PK catalyzing one of the final steps of the Embden-Meyerhof pathway, there is no net yield of adenosine triphosphate (ATP) during glycolysis, the sole source of energy production required for proper RBC function and survival. In hereditary hemolytic anemias, RBC health is compromised and therefore lifespan is shortened. Although our knowledge on glycolysis in general and PK function in particular is solid, recent advances in genetic, molecular, biochemical, and metabolic aspects of hereditary anemias have improved our understanding of these diseases. These advances provide a rationale for targeting PK as therapeutic option in hereditary hemolytic anemias other than PK deficiency. This review summarizes the knowledge, rationale, (pre)clinical trials, and future advances of PK activators for this important group of rare diseases.

激活丙酮酸激酶作为罕见溶血性贫血的治疗选择:对一种旧酶的新认识
治疗各种遗传性溶血性贫血的新进展反映了丙酮酸激酶(PK),一种糖酵解的关键酶,在红细胞(RBC)健康中的关键作用。如果没有PK催化Embden-Meyerhof途径的最后一步,糖酵解过程中就没有三磷酸腺苷(ATP)的净产量,而三磷酸腺苷是红细胞正常功能和存活所需的唯一能量来源。在遗传性溶血性贫血中,红细胞健康受到损害,因此寿命缩短。尽管我们对糖酵解,特别是PK功能的了解是扎实的,但遗传性贫血的遗传、分子、生化和代谢方面的最新进展提高了我们对这些疾病的理解。这些进展为靶向PK作为PK缺乏以外的遗传性溶血性贫血的治疗选择提供了理论依据。这篇综述总结了PK激活剂在这类重要罕见病中的知识、原理、(预)临床试验和未来进展。
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来源期刊
Blood Reviews
Blood Reviews 医学-血液学
CiteScore
13.80
自引率
1.40%
发文量
78
期刊介绍: Blood Reviews, a highly regarded international journal, serves as a vital information hub, offering comprehensive evaluations of clinical practices and research insights from esteemed experts. Specially commissioned, peer-reviewed articles authored by leading researchers and practitioners ensure extensive global coverage across all sub-specialties of hematology.
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