The remyelination effect of DNA framework nucleic acids on demyelinating diseases

Abstract

Multiple sclerosis (MS) is one of the most famous and common demyelinating diseases in young adults, characterized by motor, sensory, and cognitive impairments. In MS patients, multifocal demyelinating lesions, inflammatory infiltrates, axonal damage, and deletion of oligodendrocytes are observed. For the solely immunomodulatory focus has exhibited unsatisfactory ability to combat the progression of MS disability. There is an absence of first-line drugs against MS to delay the progression and obtain clinical improvement. Tetrahedral framework nucleic acids (tFNAs), novel self-assembled nucleic-acid nanomaterials, have been found to exhibit broad application value. Previous studies have reported positive reactions between tFNAs and various cell types, and tFNAs are able to act the advantages of neuroprotective, anti-apoptosis and anti-inflammatory. To investigate a new research direction for remyelination and potential mechanism for MS therapies, we attempted to characterize the effects of tFNAs on remyelination. The results in vitro demonstrated that tFNAs were able to rescue oligodendroglial progenitor cells (OPCs) from interferon-γ (IFN-γ) induced cell death. In in vivo study, functional remyelination was assessed by behavior test and histological examination in cuprizone-induced mice treated with tFNAs. The tFNAs-treated groups exhibited excellent remyelination. Proteins related to the PI3K-AKT-mTOR and mitochondrial apoptotic pathways were examined to further support this finding. In conclusion, our study suggested the therapeutic potential of tFNAs for MS patients by enhancing the remyelination.