New Insights into Alzheimer's Disease : Novel Pathogenesis, Drug Target and Delivery
Alzheimer's disease (AD), the most common type of dementia, is characterized by senile plaques composed of amyloid β protein (Aβ) and neurofilament tangles derived from the hyperphosphorylation of tau protein. However, the developed medicines targeting Aβ and tau have not obtained ideal clinical efficacy, which raises a challenge to the hypothesis that AD is Aβ cascade-induced. A critical problem of AD pathogenesis is which endogenous factor induces Aβ aggregation and tau phosphorylation. Recently, age-associated endogenous formaldehyde has been suggested to be a direct trigger for Aβ- and tau-related pathology. Another key issue is whether or not AD drugs are successfully delivered to the damaged neurons. Both the blood-brain barrier (BBB) and extracellular space (ECS) are the barriers for drug delivery. Unexpectedly, Aβ-related SP deposition in ECS slows down or stops interstitial fluid drainage in AD, which is the direct reason for drug delivery failure. Here, we propose a new pathogenesis and perspectives on the direction of AD drug development and drug delivery: (1) aging-related formaldehyde is a direct trigger for Aβ assembly and tau hyperphosphorylation, and the new target for AD therapy is formaldehyde; (2) nano-packaging and physical therapy may be the promising strategy for increasing BBB permeability and accelerating interstitial fluid drainage.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Pharmaceutics - 15(2023), 4 vom: 03. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Haishu [VerfasserIn] |
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| Links: |
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| Themen: |
Alzheimer’s disease |
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| Anmerkungen: |
Date Revised 01.05.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/pharmaceutics15041133 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356151956 |
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| 520 | |a Alzheimer's disease (AD), the most common type of dementia, is characterized by senile plaques composed of amyloid β protein (Aβ) and neurofilament tangles derived from the hyperphosphorylation of tau protein. However, the developed medicines targeting Aβ and tau have not obtained ideal clinical efficacy, which raises a challenge to the hypothesis that AD is Aβ cascade-induced. A critical problem of AD pathogenesis is which endogenous factor induces Aβ aggregation and tau phosphorylation. Recently, age-associated endogenous formaldehyde has been suggested to be a direct trigger for Aβ- and tau-related pathology. Another key issue is whether or not AD drugs are successfully delivered to the damaged neurons. Both the blood-brain barrier (BBB) and extracellular space (ECS) are the barriers for drug delivery. Unexpectedly, Aβ-related SP deposition in ECS slows down or stops interstitial fluid drainage in AD, which is the direct reason for drug delivery failure. Here, we propose a new pathogenesis and perspectives on the direction of AD drug development and drug delivery: (1) aging-related formaldehyde is a direct trigger for Aβ assembly and tau hyperphosphorylation, and the new target for AD therapy is formaldehyde; (2) nano-packaging and physical therapy may be the promising strategy for increasing BBB permeability and accelerating interstitial fluid drainage | ||
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| 700 | 1 | |a Xu, Jinan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Hanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Tiancheng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yihao |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Shentu, Yangping |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Zhiqian |e verfasserin |4 aut | |
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