Wenqiang Qian, Daozhou Liu, Jie Liu, Miao Liu, Qifeng Ji, Bangle Zhang, Zhifu Yang, Ying Cheng, Siyuan Zhou
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引用次数: 0
Abstract
Mitochondrial dysfunction plays an important role in neuroinflammation and cognitive impairment in Alzheimer's disease (AD). Herein, this work designs a mitochondria-targeted micelle CsA-TK-SS-31 (CTS) to block the progression of AD by simultaneously alleviating mitochondrial dysfunction in microglia and neurons. The mitochondria-targeted peptide SS-31 drives cyclosporin A (CsA) to penetrate the blood-brain barrier (BBB) and delivers CsA to mitochondria of microglia and neurons in the brains of 5 × FAD mice. Under the high level of reactive oxygen species (ROS) environment in damaged mitochondria of microglia and neurons, the linker (thioketal, TK) between CsA and SS-31 is broken and CsA and SS-31 are released while consuming ROS in the microenvironment. The released CsA and SS-31 synergistically restore the mitochondrial membrane potential and the balance between the fission and fusion of mitochondria, which subsequently protect neurons from apoptosis and reduce the activation of microglia in the brains of 5 × FAD mice. Ultimately, the neuroinflammation and cognitive impairment of 5 × FAD mice are ameliorated. This research provides a synergistic treatment strategy for AD through alleviating mitochondrial dysfunction to reduce neuroinflammation and restore the function of neurons simultaneously.
期刊介绍:
Small serves as an exceptional platform for both experimental and theoretical studies in fundamental and applied interdisciplinary research at the nano- and microscale. The journal offers a compelling mix of peer-reviewed Research Articles, Reviews, Perspectives, and Comments.
With a remarkable 2022 Journal Impact Factor of 13.3 (Journal Citation Reports from Clarivate Analytics, 2023), Small remains among the top multidisciplinary journals, covering a wide range of topics at the interface of materials science, chemistry, physics, engineering, medicine, and biology.
Small's readership includes biochemists, biologists, biomedical scientists, chemists, engineers, information technologists, materials scientists, physicists, and theoreticians alike.