Parkinson's disease (PD) is considered as a high prevalence neurodegenerative disorders worldwide. Pathologically, the demise of dopamine-producing cells, in large part due to an abnormal accumulation of the α-synuclein in the substantia nigra, is one of the main causes of the disease. Up until now, many de novo investigations have been conducted to disclose the mechanisms underlying in PD. Among them, impacts of non-coding RNAs (ncRNAs) on the pathogenesis and/or progression of PD need to be highlighted. microRNAs (miRNAs) and long ncRNAs (lncRNAs) are more noteworthy in this context. miRNAs are small ncRNAs (with 18-25 nucleotide in length) that control the expression of multiple genes at post-transcriptional level, while lncRNAs have longer size (over 200 nucleotides) and are involved in some key biological processes through various mechanisms. Involvement of miRNAs has been well documented in the development of PD, particularly gene expression. Hence, in this current review, we will discuss the impacts of miRNAs in regulation of the expression of PD-related genes and the role of lncRNAs in the pathogenesis of PD.
The science of gene therapy has experienced a controversial history. At first, the initial concept that various disorders become curable by gene transferring was very exciting and challengeable. However, the problems and difficulties related to emerging techniques and unwanted side effects seen in some patients who have undergone gene therapy make some questions against the safety of novel molecular medicine approach. In line with this statement, discovery and developing a good bio-vector possessing low toxicity and high efficiency rate are the most important issues in gene therapy field. Introducing exosomes as vectors for gene delivery gives us a new opportunity in gene-based therapy. Exosomes, ranging from 30 to 120 nm in diameter, have unique lipid and protein composition. These nanostructures participate in cell-to-cell cross-talk, regulation of immune system, and the transport of genetic material. Besides the inherent potency of exosomes in gene therapy, a better understanding of their biology, characteristics, production, targeting, and cargo loading still need to be elucidated. In the current review, we exclusively focused on the various facets of exosomes and their importance as a bio-shuttle in gene therapy.
Up to present, many advantages have been achieved in the field of cell-based therapies by applying sophisticated methodologies and delivery approaches. Microcapsules are capable to provide safe microenvironment for cells during transplantation in a simulated physiological 3D milieu. Here, we aimed to investigate the effect of alginate-gelatin encapsulation on angiogenic behavior of human endothelial cells over a period of 5 days. Human umbilical vein endothelial cells were encapsulated by alginate-gelatin substrate and incubated for 5 days. MTT and autophagy PCR array analysis were used to monitor cell survival rate. For in vitro angiogenesis analysis, cell distribution of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 were detected by ELISA. In addition to in vitro tubulogenesis assay, we monitored the expression of VE-cadherin by Western blotting. The migration capacity of encapsulated HUVECs was studied by measuring MMP-2 and MMP-9 via gelatin zymography. The in vivo angiogenic potential of encapsulated HUVECs was analyzed in immune-compromised mouse implant model during 7 days post-transplantation. We demonstrated that encapsulation promoted HUVECs cell survival and proliferation. Compared to control, no significant differences were observed in autophagic status of encapsulated cells (p > 0.05). The level of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 were increased, but did not reach to significant levels. Encapsulation decreased MMP-2, -9 activity and increased the VE-cadherin level in enclosed cells (p < 0.05). Moreover, an enhanced in vivo angiogenic response of encapsulated HUVECs was evident as compared to non-capsulated cells (p < 0.05). These observations suggest that alginate-gelatin encapsulation can induce angiogenic response in in vivo and in vitro conditions.
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