Restoring Soluble Amyloid Precursor Protein α Functions as a Potential Treatment for Alzheimer's Disease.
Restoring Soluble Amyloid Precursor Protein α Functions as a Potential Treatment for Alzheimer's Disease.
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DOI：
10.1002/jnr.23823
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发表时间：
2017-04
影响因子：
4.2
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Habib A;Sawmiller D;Tan J
可溶性淀粉样前体蛋白α (sAPPα)是非淀粉样原性淀粉样前体蛋白（APP）加工过程中分泌的蛋白水解片段，具有多种神经保护功能。这些功能包括但不限于细胞培养和动物模型中的增殖、神经保护、突触可塑性、记忆形成、神经发生和神经胚胎发生。此外，sAPPα通过直接调节APP β分泌酶蛋白水解以及Aβ相关或不相关的tau病理（阿尔茨海默病（AD）的标志性病理）影响淀粉样蛋白-β (Aβ)的产生。因此，通过增加非淀粉样变性APP加工和/或操纵其信号传导来恢复大脑中sAPPα水平和功能可以减少AD病理和认知障碍。大脑中sAPPα受体、下游效应物和信号通路的鉴定和表征可能会为阿尔茨海默病预防或干预的治疗靶点铺平道路。
Soluble amyloid precursor protein α (sAPPα), a secreted proteolytic fragment of non-amyloidogenic amyloid precursor protein (APP) processing, is known for numerous neuroprotective functions. These functions include but are not limited to proliferation, neuroprotection, synaptic plasticity, memory formation, neurogenesis and neuritogenesis in cell culture and animal models. In addition, sAPPα influences amyloid-β (Aβ) production by direct modulation of APP β-secretase proteolysis as well as Aβ-related or unrelated tau-pathology, hallmark pathologies of Alzheimer’s disease (AD). Thus, the restoration of sAPPα levels and functions in the brain by increasing non-amyloidogenic APP processing and/or manipulation of its signaling could reduce AD pathology and cognitive impairment. It is likely that identification and characterization of sAPPα receptors in the brain, downstream effectors, and signaling pathways will pave the way for an attractive therapeutic target for AD prevention or intervention.