Combining Multifunctional Delivery System with Blood-Brain Barrier Reversible Opening Strategy for the Enhanced Treatment of Alzheimer's Disease
© 2023 Wiley‐VCH GmbH..
Alzheimer's disease (AD) is a neurodegenerative illness characterized by intracellular tau-phosphorylation, β-amyloid (Aβ) plaques accumulation, neuroinflammation, and impaired behavioral ability. Owing to the lack of effective brain delivery approaches and the presence of the blood-brain barrier (BBB), current AD therapeutic endeavors are severely limited. Herein, a multifunctional delivery system (RVG-DDQ/PDPsiBACE1) is elaborately combined with a protein kinase B (AKT) agonist (SC79) for facilitating RVG-DDQ/PDP@siBACE1 to target and penetrate BBB, enter brain parenchyma, and further accumulate in AD brain lesion. Moreover, compared with the unitary dose of RVG-DDQ/PDP@siBACE1, this collaborative therapy strategy exhibits a distinctive synergistic function including scavenging reactive oxygen species (ROS), decreasing of Aβ production, alleviating neuroinflammation by promoting the polarized microglia into the anti-inflammatory M2-like phenotype and significantly enhancing the cognitive functions of AD mice. More strikingly, according to these results, an innovative signaling pathway "lncRNA MALAT1/miR-181c/BCL2L11" is found that can mediate the neuronal apoptosis of AD. Taken together, combining the brain targeted delivery system with noninvasive BBB opening can provide a promising strategy and platform for targeting treatment of AD and other neurodegenerative diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Advanced healthcare materials - 13(2024), 8 vom: 31. März, Seite e2302939 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ke, Jia [VerfasserIn] |
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| Links: |
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| Themen: |
Alzheimer's disease |
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| Anmerkungen: |
Date Completed 28.03.2024 Date Revised 28.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/adhm.202302939 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366077643 |
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| 520 | |a Alzheimer's disease (AD) is a neurodegenerative illness characterized by intracellular tau-phosphorylation, β-amyloid (Aβ) plaques accumulation, neuroinflammation, and impaired behavioral ability. Owing to the lack of effective brain delivery approaches and the presence of the blood-brain barrier (BBB), current AD therapeutic endeavors are severely limited. Herein, a multifunctional delivery system (RVG-DDQ/PDPsiBACE1) is elaborately combined with a protein kinase B (AKT) agonist (SC79) for facilitating RVG-DDQ/PDP@siBACE1 to target and penetrate BBB, enter brain parenchyma, and further accumulate in AD brain lesion. Moreover, compared with the unitary dose of RVG-DDQ/PDP@siBACE1, this collaborative therapy strategy exhibits a distinctive synergistic function including scavenging reactive oxygen species (ROS), decreasing of Aβ production, alleviating neuroinflammation by promoting the polarized microglia into the anti-inflammatory M2-like phenotype and significantly enhancing the cognitive functions of AD mice. More strikingly, according to these results, an innovative signaling pathway "lncRNA MALAT1/miR-181c/BCL2L11" is found that can mediate the neuronal apoptosis of AD. Taken together, combining the brain targeted delivery system with noninvasive BBB opening can provide a promising strategy and platform for targeting treatment of AD and other neurodegenerative diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alzheimer's disease | |
| 650 | 4 | |a BCL2L11 | |
| 650 | 4 | |a blood–brain barrier | |
| 650 | 4 | |a delivery system | |
| 650 | 4 | |a neuroinflammation | |
| 650 | 7 | |a Amyloid beta-Peptides |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 700 | 1 | |a Yu, Caini |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Sufen |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Yiling |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yichong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Ping, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Fuqiang |e verfasserin |4 aut | |
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