BACE1 Physiological Functions May Limit Its Use as Therapeutic Target for Alzheimer's Disease

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• 作者：Soraia Barã ; o¹ ; ² ; Diederik Moechars³ ; Stefan F. Lichtenthaler⁴ ; ⁵ ; Bart De Strooper¹ ; ² ; ⁶ ; ^{Bart.DeStrooper@cme.vib-kuleuven.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BACE1 ; Alzheimer's disease ; therapeutic target ; APP ; C-terminal fragments
• 刊名：Trends in Neurosciences
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：39
• 期：3
• 页码：158-169
• 全文大小：2208 K

文摘

The protease β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is required for the production of the amyloid-β (Aβ) peptide, which is central to the pathogenesis of Alzheimer's disease (AD). Chronic inhibition of this protease may temper amyloid production and cure or prevent AD. However, while BACE1 inhibitors are being pushed forward as drug candidates, a remarkable gap in knowledge on the physiological functions of BACE1 and its close homolog BACE2 becomes apparent. Here we discuss the major discoveries of the past 3 years concerning BACE1 biology and to what extent these could limit the use of BACE1 inhibitors in the clinic.