2. Academic Validation
  3. Engineered Extracellular Vesicles with SHP2 High Expression Promote Mitophagy for Alzheimer's Disease Treatment

Engineered Extracellular Vesicles with SHP2 High Expression Promote Mitophagy for Alzheimer's Disease Treatment

  • Adv Mater. 2022 Oct 4;e2207107. doi: 10.1002/adma.202207107.
Fang Xu 1,  Yi Wu 1,  Qianyu Yang 1,  Ying Cheng 2,  Jialu Xu 1,  Yue Zhang 1,  Huaxing Dai 1,  Beilei Wang 1,  Qingle Ma 1,  Yitong Chen 1,  Fang Lin 2,  Chao Wang 1
Affiliations

Affiliations

  • 1 Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu, 215123, PR China.
  • 2 Institute of Pharmacology, Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Neuropsychiatric Disease, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, 215123, China.
PMID: 36193769 DOI: 10.1002/adma.202207107
Abstract

Mitochondrial dysfunction is a fundamental pathological feature of Alzheimer's disease (AD). However, toxicity and poor brain enrichment of existing Mitophagy inducers limit their further applications. In this study, we develops a platform for AD therapy using nanosized mesenchymal stem cells-derived extracellular vesicles with tyrosine phosphatase-2 (SHP2) high-expression (MSC-EVs-SHP2). The high blood-brain barrier penetration ability of MSC-EVs-SHP2 is demonstrated in AD-mice, facilitating SHP2 delivery to the brain. In addition, MSC-EVs-SHP2 significantly induces Mitophagy of neuronal cells, which alleviates mitochondrial damage-mediated Apoptosis and NLRP3 inflammasome activation. Mitophagy further diminishes neuronal cells Apoptosis and neuroinflammation, culminating with rescued synaptic loss and cognitive decline in an AD mouse model. Our EV-engineering technology provide a potential platform for effective AD therapy by inducing Mitophagy. This article is protected by copyright. All rights reserved.

Keywords

Alzheimer's disease; Engineered extracellular vesicle; SHP2; mitophagy.

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