| 张云莎 郭茂娟 李虎虎 姜希娟 杜欢.Aβ的外周清除与阿尔茨海默病[J].,2016,16(22):4398-4400 |
| Aβ的外周清除与阿尔茨海默病 |
| Peripherocial Clearance of Amyloid-Beta in Alzheimer’s Disease |
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| DOI： |
| 中文关键词: 阿尔茨海默病 β-淀粉样蛋白 外周清除 |
| 英文关键词: Alzheimer's disease Amyloid-beta Peripheral clearance |
| 基金项目: |
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| 中文摘要: |
| 脑β- 淀粉样蛋白（Amyloid-β，Aβ）沉积是阿尔茨海默病（Alzheimer's disease, AD）发病的核心问题。Aβ的沉积与其生成和
清除失衡有关，尤其是清除障碍是导致A茁沉积的主要原因。Aβ经RAGE, LRP1 及P-gp 介导跨血脑屏障（blood -brain barrier,
BBB）转运至外周和经血管旁淋巴引流途径到达局部淋巴结是脑Aβ转运至外周进而发挥外周清除效应的两条途径，亦是Aβ清
除的主要途径。RAGE, LRP1 及P-gp 表达异常、血管旁淋巴引流途径受阻及外周清除组织功能障碍均会影响A茁外周清除，促进
AD病程的进展。因此干预BBB上转运体的功能及血管旁淋巴引流通路，实现外周组织的清除效应，有利于A茁外周清除。随着
外周Aβ清除，脑A茁则会源源不断转运至外周，发挥外周降解效应，即外周Sink 效应。基于外周Sink 效应，将AD治疗重点由促
进Aβ脑内清除转为外周清除将是一条有效且相对安全的途径。 |
| 英文摘要: |
| Aggregation and accumulation of amyloid-β peptide ( Aβ) in brain tissues play pivotal and causal roles in the
pathogenesis of AD and has since become the major therapeutic target for this disease. The cause of the accumulation of Aβ may be due
to faulty clearance of Aβ frombrain. Aβ transport across the blood -brain barrier (BBB) frombrain to blood and perivascular drainage of
Aβto lymph nodes are the major pathways of Aβ clearance. Regulating RAGE, LRP-1and P-gp, are the main transporters on the BBB,
and maintaining the function of peripheral tissues can inprove Aβperipheral clearance, hence to reduce brain A茁. Considering the
limitated delivery of drugs across the BBB and adverse effects of immuno-therapies targeting the central clearance of amyloid plaques,
we propose that therapies to restore the peripheral Aβ'Sink' action, hold potential to reduce brain Aβare effective and safe. |
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