Department of Pathology, University of Melbourne, Parkville, Australia.
Int J Biochem Cell Biol. 2010 Dec;42(12):1923-6. doi: 10.1016/j.biocel.2010.08.017. Epub 2010 Sep 15.
β-Site APP-cleaving enzyme (BACE) is a membrane-bound aspartyl protease involved in the production of Alzheimer's disease (AD) Aβ amyloid peptides. This enzyme is ubiquitously expressed, with highest levels in the brain and pancreas. Its cellular trafficking is tightly controlled as it recycles between endosomes and trans-Golgi network. BACE expression increases in response to aging and various stress stimuli. It is elevated in the brain cortex of AD sufferers, and increased levels of BACE in the cerebrospinal fluid of patients with mild cognitive impairment may provide an early biomarker of AD. BACE is considered as a rational drug target for AD therapy, and inhibitors are under development. Anomalies in the behaviour and biochemistry of BACE(-/-) mice have pointed to the role this enzyme plays in the processing of neuregulin and of voltage-gated sodium channel β-subunit. A full understanding of BACE biology in health and disease is needed to establish a safe AD therapy based on BACE inhibitors.
β-位点 APP 裂解酶（BACE）是一种膜结合的天冬氨酸蛋白酶，参与阿尔茨海默病（AD）Aβ淀粉样肽的产生。这种酶广泛表达，在大脑和胰腺中表达水平最高。它的细胞运输受到严格控制，因为它在内涵体和反式高尔基体网络之间循环。BACE 的表达会随着衰老和各种应激刺激而增加。AD 患者大脑皮层中的 BACE 表达增加，轻度认知障碍患者脑脊液中 BACE 水平升高可能提供 AD 的早期生物标志物。BACE 被认为是 AD 治疗的合理药物靶点，抑制剂正在开发中。BACE(-/-) 小鼠的行为和生物化学异常表明，该酶在神经调节素和电压门控钠离子通道β亚基的加工中发挥作用。为了在 BACE 抑制剂的基础上建立安全的 AD 治疗方法，需要充分了解 BACE 在健康和疾病中的生物学特性。
