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Multifunctional peptide-assembled micelles for simultaneously reducing amyloid-β and reactive oxygen species.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Lei, Li 
Zou, Zhifeng 
Liu, Jin 
Fu, Ying 

Abstract

The excessive production and deposition of amyloid-β (Aβ) is one of the most important etiologies of Alzheimer's disease (AD). The interaction between Aβ and metal ions produces aberrant reactive oxygen species (ROS), which induce oxidative stress and accelerate the progression of AD. To reduce Aβ plaques and ROS to maintain their homeostasis is an emerging and ingenious strategy for effective treatment of AD. Herein, we report the rational design of multifunctional micelles (MPGLT) based on a polymer-grafted peptide to simultaneously clear Aβ and ROS for AD therapy. The MPGLT integrating three functional peptides as a ROS scavenger (tk-GSH), β-sheet breaker (LP) and an autophagy activator (TK) respectively, could capture and degrade Aβ. Meanwhile, the tk-GSH on the surface of MPGLT effectively scavenges the intracellular ROS. Consequently, MPGLT reduced the cytotoxicity of Aβ and ROS. In vivo animal studies using an AD mouse model further showed that MPGLT could transport across the blood-brain barrier for decreasing the Aβ plaque and eliminating ROS in vivo. This peptide micelle-based synergistic strategy may provide novel insight for AD therapy.

Description

Keywords

34 Chemical Sciences, Acquired Cognitive Impairment, Neurodegenerative, Aging, Neurosciences, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Brain Disorders, Neurological

Journal Title

Chem Sci

Conference Name

Journal ISSN

2041-6520
2041-6539

Volume Title

12

Publisher

Royal Society of Chemistry (RSC)