Neuroprotective and Neurotherapeutic Effects of Tetrahedral Framework Nucleic Acids on Parkinson’s Disease in Vitro

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease characterized by a series of progressive motor disorders. PD is caused by dysfunction of basal ganglia, decrease of dopaminergic neurons in substantia nigra, and abnormal accumulation of Lewy bodies and Lewy neurites. Antiparkinsonian agents, which are currently used for treatment of PD, exhibit unsatisfactory effects on disease control. In recent years, tetrahedral framework nucleic acids (TFNAs) have been considered as multifunctional nanomaterials, and their scope of application has been extended to a wide range of areas. In previous studies, TFNAs were shown to exert positive effects on various cell types in processes such as cell proliferation, cell differentiation, and apoptosis. In the present study, we explored the role of TFNAs in the treatment and prevention of PD in vitro and elucidated its underlying mechanisms of action. On the basis of the experiments conducted, we demonstrated that TFNAs could inhibit and repair the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of PC12 cells through decreasing the accumulation of α-synuclein, one of the characteristic biomarkers of PD. Genes and proteins related to the AKT/PI3K signaling and mitochondrial apoptotic pathways were examined to further support this finding. Most importantly, TFNAs exhibited unexpected neuroprotective and neurorestorative effects on PC12 cells, providing a novel approach for reducing the neuropathological changes caused by PD.

Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway

“…Previous studies have indicated that tFNAs can promote the proliferation of various cell types. 24 – 27 , 29 , 34 , 35 Therefore, in this research, we aimed to determine whether this type of effect also existed in HaCaT and HSF cells. CCK-8 assays were used to examine cell proliferation, while cell-cycle assays were used to analyze changes in the number of cells at each stage.…”

“…As shown in previous studies, tFNAs are able to promote cell migration. 27 – 29 , 35 Scratch experiments are widely performed to investigate cell migration in vitro, but there are still factors that can interfere with these outcomes. In this study, to minimize variability, all scratches were made by the same person.…”

“… 24 – 26 Previous studies have demonstrated that tFNAs have the capacity to provoke cell proliferation and migration and to reduce inflammatory reactions. 27 – 30 In addition, tFNAs may influence different signaling pathways, such as the Wnt pathway and the Nrf2 pathway. 27 , 28 However, to the best of our knowledge, there have been few reports regarding nucleic-acid nanophase materials that directly affect the skin wound healing process without delivery assistance.…”

“… 27 – 30 In addition, tFNAs may influence different signaling pathways, such as the Wnt pathway and the Nrf2 pathway. 27 , 28 However, to the best of our knowledge, there have been few reports regarding nucleic-acid nanophase materials that directly affect the skin wound healing process without delivery assistance. In this study, we focused on evaluating the effects of tFNAs on keratinocytes (HaCaT cell line) and fibroblasts(HSF cell line) in vitro and in rat wound models in vivo.…”

Rationally Programming Nanomaterials with DNA for Biomedical Applications

“…By employing the pH-responsive i-motif DNA locking strands in the rectangular DNA nanosheet during its reconfiguration process, Ding and co-workers reported a rectangular DNA nanosheet-based nanodevice vaccine for cancer immunotherapy very recently. [214] www.advancedsciencenews.com www.advancedscience.com In addition to cancer therapy, the DNA-based nanostructures were also widely explored for the treatment of alleviating acute kidney injury, [170] wound healing, [215] Parkinson's disease, [216] and other diseases. [217][218][219][220]…”