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标题:Clearance of Amyloid Beta and Tau in Alzheimer's Disease: from Mechanisms to Therapy.
时间:2020-02-15 10:52:45
DOI:10.1007/s12640-018-9895-1
PMID:29626319
作者:Shu-Hui;Xin;Lin
关键词:Alzheimer’s;disease;Amyloid-beta;Blood;circulatory;clearance;Lymphatic;clearance;Peripheral;clearance;Tau
摘要:Alzheimer's disease (AD) is the most common neurodegenerative disease. Pathological proteins of AD mainly contain amyloid-beta (Aβ) and tau. Their deposition will lead to neuron damage by a series of pathways, and then induce memory and cognitive impairment. Thus, it is pivotal to understand the clearance pathways of Aβ and tau in order to delay or even halt AD. Aβ clearance mechanisms include ubiquitin-proteasome system, autophagy-lysosome, proteases, microglial phagocytosis, and transport from the brain to the blood via the blood-brain barrier (BBB), arachnoid villi and blood-CSF barrier, which can be named blood circulatory clearance. Recently, lymphatic clearance has been demonstrated to play a key role in transport of Aβ into cervical lymph nodes. The discovery of meningeal lymphatic vessels is another direct evidence for lymphatic clearance in the brain. Furthermore, periphery clearance also contributes to Aβ clearance. Tau clearance is almost the same as Aβ clearance. In this review, we will mainly introduce the clearance mechanisms of Aβ and tau proteins, and summarize corresponding targeted drug therapies for AD.
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目录:
  • Clearance of Amyloid Beta and Tau in Alzheimer’s Disease: from Mechanisms to Therapy
    • Abstract
    • Introduction
    • The Protein Clearance Machinery
      • Degradation in Brain
      • Transport into Periphery
        • Blood Circulatory Clearance of Central Nervous System
        • Lymphatic Clearance of Central Nervous System
      • Peripheral Clearance
    • Protein Clearance in Alzheimer’s Disease
      • Clearance of Amyloid-Beta
        • Ubiquitin–Proteasome System and Autophagy-Lysosome
        • Proteases
        • Microglial Phagocytosis
        • Blood-Brain Barrier
        • Blood-Cerebrospinal Fluid Barrier
        • Perivascular Drainage of Interstitial Fluid
        • Glymphatic Drainage of Interstitial Fluid
        • Lymphatic Drainage of Cerebrospinal Fluid
        • Clearance in the Liver and Kidney
        • Clearance in Red Blood Cells and Monocytes
      • Clearance of Tau
        • Ubiquitin–Proteasome System and Autophagy-Lysosome
        • Proteases
        • Microglial Phagocytosis
        • Blood Circulatory Clearance and Lymphatic Clearance
        • Peripheral Clearance
    • Therapeutic Targeting Amyloid-Beta and Tau Clearance in AD
      • Targeting Ubiquitin-Proteasome System
      • Targeting Autophagy-Lysosome System
      • Targeting Proteases
      • Targeting Microglial Phagocytosis
      • Targeting Blood-Brain Barrier Transporters
      • Targeting Perivascular Drainage
      • Targeting Peripheral Clearance
      • Other Alternative Methods for Clearing Amyloid-Beta and Tau
    • Concluding Remarks and Future Perspectives
    • References

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