Department of Microbiology, Immunology, and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9177, Morgantown, WV, 26506, USA.
Department of Neuroscience, Emergency Medicine, and Microbiology, Immunology and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9303, Morgantown, WV, 26506, USA.
Metab Brain Dis. 2019 Feb;34(1):3-19. doi: 10.1007/s11011-018-0322-3. Epub 2018 Oct 4.
Stroke is the fifth leading cause of death in the U.S., with more than 100,000 deaths annually. There are a multitude of risks associated with stroke, including aging, cardiovascular disease, hypertension, Alzheimer's disease (AD), and immune suppression. One of the many challenges, which has so far proven to be unsuccessful, is the identification of a cost-effective diagnostic or prognostic biomarker for stroke. Alkaline phosphatase (AP), an enzyme first discovered in the 1920s, has been evaluated as a potential biomarker in many disorders, including many of the co-morbidities associated with stroke. This review will examine the basic biology of AP, and its most common isoenzyme, tissue nonspecific alkaline phosphatase (TNAP), with a specific focus on the central nervous system. It examines the preclinical and clinical evidence which supports a potential role for AP in stroke and suggests potential mechanism(s) of action for AP isoenzymes in stroke. Lastly, the review speculates on the clinical utility of AP isoenzymes as potential blood biomarkers for stroke or as AP-targeted treatments for stroke patients.
中风是美国第五大致死原因,每年有超过 10 万人死亡。中风与多种风险相关,包括衰老、心血管疾病、高血压、阿尔茨海默病(AD)和免疫抑制。迄今为止,尚未成功确定一种具有成本效益的中风诊断或预后生物标志物,这是众多挑战之一。碱性磷酸酶(AP)是 20 世纪 20 年代首次发现的一种酶,已在许多疾病中被评估为一种潜在的生物标志物,包括许多与中风相关的合并症。本综述将检查 AP 的基本生物学及其最常见的同工酶组织非特异性碱性磷酸酶(TNAP),特别关注中枢神经系统。它检查了支持 AP 在中风中具有潜在作用的临床前和临床证据,并提出了 AP 同工酶在中风中作用的潜在机制。最后,综述推测 AP 同工酶作为中风潜在血液生物标志物或作为中风患者的 AP 靶向治疗的临床实用性。