دورية أكاديمية
أعرض في EDS

Modulating autophagic flux via ROS-responsive targeted micelles to restore neuronal proteostasis in Alzheimer's disease.

التفاصيل البيبلوغرافية
العنوان: Modulating autophagic flux via ROS-responsive targeted micelles to restore neuronal proteostasis in Alzheimer's disease.
المؤلفون: Xu S; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Yang P; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Qian K; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Li Y; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Guo Q; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Wang P; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Meng R; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Wu J; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Cao J; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Cheng Y; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Xu M; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China., Zhang Q; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China.
المصدر: Bioactive materials [Bioact Mater] 2021 Oct 04; Vol. 11, pp. 300-316. Date of Electronic Publication: 2021 Oct 04 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Ke Ai Publishing Country of Publication: China NLM ID: 101685294 Publication Model: eCollection Cited Medium: Internet ISSN: 2452-199X (Electronic) Linking ISSN: 2452199X NLM ISO Abbreviation: Bioact Mater Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Beijing : Ke Ai Publishing
مستخلص: Compromised autophagy and defective lysosomal clearance significantly contribute to impaired neuronal proteostasis, which represents a hallmark of Alzheimer's disease (AD) and other age-related neurodegenerative disorders. Growing evidence has implicated that modulating autophagic flux, instead of inducing autophagosome formation alone, would be more reliable to rescue neuronal proteostasis. Concurrently, selectively enhancing drug concentrations in the leision areas, instead of the whole brain, will maximize therapeutic efficacy while reduing non-selective autophagy induction. Herein, we design a ROS-responsive targeted micelle system (TT-NM/Rapa) to enhance the delivery efficiency of rapamycin to neurons in AD lesions guided by the fusion peptide TPL, and facilitate its intracellular release via ROS-mediated disassembly of micelles, thereby maximizing autophagic flux modulating efficacy of rapamycin in neurons. Consequently, it promotes the efficient clearance of intracellular neurotoxic proteins, β-amyloid and hyperphosphorylated tau proteins, and ameliorates memory defects and neuronal damage in 3 × Tg-AD transgenic mice. Our studies demonstrate a promising strategy to restore autophagic flux and improve neuronal proteostasis by rationally-engineered nano-systems for delaying the progression of AD.
Competing Interests: The authors declare no conflict of interest.
(© 2021 The Authors.)
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فهرسة مساهمة: Keywords: Alzheimer's disease; Autophagic flux; Brain-neuron targeting; ROS-Responsive micelle system; Rapamycin
تواريخ الأحداث: Date Created: 20220103 Latest Revision: 20220104
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8668445
DOI: 10.1016/j.bioactmat.2021.09.017
PMID: 34977433
قاعدة البيانات: MEDLINE
الوصف
تدمد:2452-199X
DOI:10.1016/j.bioactmat.2021.09.017