Abstract
Effective treatments for neurodegenerative diseases need to be developed. MiR132 is abundantly expressed in the brain, and it modulates neuron morphology and plays a key role in maintaining neuron survival. Regulating miR132 can effectively improve the symptoms of Alzheimer’s disease. It can also reduce cell death after cerebral hemorrhage, improve the microenvironment of hematoma lesions and provide a certain protective effect from brain damage after cerebral ischemia. MiR132 has great potential in the treatment of cerebral ischemia and Alzheimer’s disease. To prevent the decline of miR132 of miR132 levels in the blood, we used mouse and rat models of Alzheimer’s disease with ischemic brain injury, and then delivered Wheat germ agglutinin (WGA)-NPs-miR132 intranasally to treat neurological damage after cerebral ischemia. Synaptic protein expression levels in Alzheimer’s mouse models increased significantly after administration. We propose that, nasal delivery of WGA-NPs-miR132 is an interesting novel therapeutic approach for the treatment of neurodegenerative diseases.
Highlights
Many drugs have been developed for treating central nervous system diseases, their therapeutic effects are still insufficient (Gitler et al, 2017)
Gene therapy has attracted widespread attention in recent years, and studies have shown that many microRNAs in mammalian brains have dynamic functions in regulating biochemical pathways; the pathogenesis of neurodegenerative diseases can be associated with disrupted miRNA regulation, which may be caused by the disruption of a single miRNA or a miRNA family, so miRNA-based treatment of neurodegenerative disease has great potential (Karnati et al, 2015; Ferrante and Conti, 2017). miRNA mimics or inhibitors can be used to restore the normal function of specific miRNAs to achieve the purpose of neurodegenerative diseases (Pereira et al, 2017)
We developed Wheat germ agglutinin (WGA)-modified PEGPLA nanoparticle with miR132 (WGA-NPs-miR132) for nasal delivery, and the neuroprotective effect of this method on Alzheimer’s disease (AD) model mice was evaluated by water maze tests and immunofluorescence analysis
Summary
Many drugs have been developed for treating central nervous system diseases, their therapeutic effects are still insufficient (Gitler et al, 2017). MiRNAs have been studied as treatments for diseases, but various therapeutic nucleic acid drugs cannot completely penetrate the blood–brain barrier (BBB) and enter brain tissues within an effective time window (Begley, 2004; Pardridge, 2005). As a potential platform for drug and gene delivery, nanoparticles have attracted great attention (Graff and Pollack, 2003) Due to their unique size, shape and surface characteristics, low biotoxicity and good biocompatibility, nanoparticles are able to protect therapeutic drugs from degradation by various degradants and enhance the concentrations of drug delivery. Wheat germ agglutinin (WGA) has been reported to bind specific oligosaccharides in nasal epithelial cells, prolonging their residence time and promoting their internalization (Lehr, 2000; Shen et al, 2011) This selective affinity for the nasal mucosa is thought to enhance the delivery of WGA-modified nanoparticles from the nose to the brain (Liu et al, 2012). The results indicated that miR132 inhaled through the nose had great potential for neuroprotection in Alzheimer’s disease and cerebral ischemia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
