Parkinson's disease (PD) is one of the most prevalent forms of synucleinopathies, and it is characterized neuropathologically by the presence of intracellular inclusions composed primarily of the protein Î±-synuclein (Î±-syn) in neurons. The previous immunotherapy targeting the Î±-syn in PD models with monoclonal antibodies has established Î±-syn protein as an effective target for neuronal cell death. However, due to the essential weaknesses of antibody and the unique features of aptamers, the aptamers could represent a promising alternative to the currently used antibodies in immunotherapy for PD. In this study, the purified human Î±-syn was used as the target for in vitro selection of aptamers using systematic evolution by exponential enrichment. This resulted in the identification of two 58-base DNA aptamers with a high binding affinity and good specificity to the Î±-syn, with KD values in the nanomolar range. Both aptamers could effectively reduce Î±-syn aggregation in vitro and in cells and target the Î±-syn to intracellular degradation through the lysosomal pathway. These effects consequently rescued the mitochondrial dysfunction and cellular defects caused by Î±-syn overexpression. To our knowledge, this is the first study to employ aptamers to block the aberrant cellular effects of the overexpressed Î±-syn in cells.
Molecular Therapy - Nucleic Acids
Digital Object Identifier (DOI)
Zheng, Yuan; Qu, Jing; Xue, Fenqin; Zheng, Yan; Yang, Bo; Chang, Yongchang; Yang, Hui; and Zhang, Jianliang, "Novel DNA Aptamers for Parkinson’s Disease Treatment Inhibit a-Synuclein Aggregation and Facilitate its Degradation" (2018). Translational Neuroscience. 62.