β-Amyloid (Aβ) is a hallmark peptide of Alzheimer's disease (AD). Herein, we explored the mechanism underlying the cytotoxicity of this peptide. Double treatment with oligomeric 42-amino-acid Aβ (Aβ42) species, which are more cytotoxic than other conformers such as monomers and fibrils, resulted in increased cytotoxicity. Under this treatment condition, an increase in intracellular localization of the peptide was observed, which indicated that the peptide administered extracellularly entered the cells. The cell-permeable peptide TAT-tagged Aβ42 (tAβ42), which was newly prepared for the study and found to be highly cell-permeable and soluble, induced Aβ-specific lamin protein cleavage, caspase-3/7-like DEVDase activation, and high cytotoxicity (5-10-fold higher than that induced by the wild-type oligomeric preparations). Oligomeric species enrichment and double treatment were not necessary for enhancing the cytotoxicity and intracellular location of the fusion peptide. Taiwaniaflavone, an inhibitor of the cytotoxicity of wild-type Aβ42 and tAβ42, strongly blocked the internalization of the peptides into the cells. These data imply a strong relationship between the cytotoxicity and intracellular location of the Aβ peptide. Based on these results, we suggest that agents that can reduce the cell permeability of Aβ42 are potential AD therapeutics.
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http://dx.doi.org/10.3390/life12040577 | DOI Listing |
Anticancer Agents Med Chem
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Department, Bursa, Faculty of Medicine, Medical Biology, Bursa Uludag University, Turkey.
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Department of Orthopedics, Sichuan Provincial People's Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu 610072, Sichuan, PR China; Chongqing Engineering Laboratory of Nano/Micro Biomedical Detection Technology, Chongqing University of Science and Technology, Chongqing 401331, PR China; Department of Urology, Deyang People's Hospital, Deyang 618099, Sichuan, PR China. Electronic address:
Developing effective nanoplatforms for chemo-immunotherapy to achieve enhanced tumor suppression and systemic antitumor immunity has recently received extensive attention. Herein, we formulated a multifunctional DNA sandwich nanodevice, DSWAC/siPD-L1, based on triangular DNA origami, to implement enhanced cancer chemo-immunotherapy. Taking advantage of the tumor-targeting ability of the AS1411 aptamer, DSWAC/siPD-L1 efficiently delivered doxorubicin (DOX), CpG, and siPD-L1 into tumor cells.
View Article and Find Full Text PDFNeuron
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Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address:
Autoimmune neurology is a rapidly expanding field driven by the discovery of neuroglial autoantibodies and encompassing a myriad of conditions affecting every level of the nervous system. Traditionally, autoantibodies targeting intracellular antigens are considered markers of T cell-mediated cytotoxicity, while those targeting extracellular antigens are viewed as pathogenic drivers of disease. However, recent advances highlight complex interactions between these immune mechanisms, suggesting a continuum of immunopathogenesis.
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Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China. Electronic address:
Liver fibrosis is a common pathological stage in the development of several chronic liver diseases, and early intervention can effectively reverse the developing process. Excessive reactive oxygen species (ROS) can promote the activation of hepatic stellate cells (HSCs), but existing treatments have not addressed this problem. In this study, different metal-based mesoporous polydopamine (MPDA) was prepared by the soft template method, and their free radical scavenging abilities, as well as the efficacy and safety of the carriers were investigated, so as to select Cu-coordinated MPDA (CMP) as the optimal nanocarrier.
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School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang 310007, China; Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang 310007, China. Electronic address:
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