Center for Advanced Therapeutic Strategies for Brain Disorders, Roskamp Institute, Sarasota, FL 34203, USA.
Trends Pharmacol Sci. 2013 Apr;34(4):215-25. doi: 10.1016/j.tips.2013.01.008. Epub 2013 Feb 27.
β-Secretase (BACE1, β-site APP cleaving enzyme 1) is an aspartic proteinase that has multiple functions in various physiological processes, such as cell differentiation, immunoregulation, and cell death. There is increasing evidence that changes in BACE1 activity are involved in many diseases, such as Alzheimer's disease (AD), schizophrenia, epileptic behavior, and others. However, a deeper understanding of the molecular biology of BACE1 is necessary for further exploration of cell development, immunological regulation, and disease pathogenesis. Here, we review the molecular and cellular biology of BACE1, including its enzymatic properties, structure, biosynthesis, and physiological functions to provide a new perspective and rational assessment of drugability. Lastly, we discuss proposed strategies to control BACE1 activity for possible therapeutic application.
β-分泌酶(BACE1,β 位淀粉样前体蛋白裂解酶 1)是一种天冬氨酸蛋白酶,在多种生理过程中具有多种功能,如细胞分化、免疫调节和细胞死亡。越来越多的证据表明,BACE1 活性的变化与许多疾病有关,如阿尔茨海默病(AD)、精神分裂症、癫痫行为等。然而,为了进一步探索细胞发育、免疫调节和疾病发病机制,需要更深入地了解 BACE1 的分子生物学。在这里,我们综述了 BACE1 的分子和细胞生物学,包括其酶学特性、结构、生物合成和生理功能,为药物开发提供了新的视角和合理的评估。最后,我们讨论了控制 BACE1 活性的可能治疗应用的策略。