| Autor: |
Qianqian Cao, Shilin Luo, Wei Yao, Youge Qu, Nanbu Wang, Jian Hong, Shigeo Murayama, Zhentao Zhang, Jiaxu Chen, Kenji Hashimoto, Qi Qi, Ji-chun Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 29, Iss , Pp 1-15 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1016/j.omtn.2022.05.037 |
| Popis: |
Parkinson’s disease (PD) is characterized by the formation of Lewy bodies (LBs) in the brain. LBs are mainly composed of phosphorylated and aggregated α-synuclein (α-Syn). Thus, strategies to reduce the expression of α-Syn offer promising therapeutic avenues for PD. DNA/RNA heteroduplex oligonucleotides (HDOs) are a novel technology for gene silencing. Using an α-Syn-HDO that specifically targets α-Syn, we examined whether α-Syn-HDO attenuates pathological changes in the brain of mouse models of PD. Overexpression of α-Syn induced dopaminergic neuron degeneration through inhibition of cyclic AMP-responsive-element-binding protein (CREB) and activation of methyl CpG binding protein 2 (MeCP2), resulting in brain-derived neurotrophic factor (BDNF) downregulation. α-Syn-HDO exerted a more potent silencing effect on α-Syn than α-Syn-antisense oligonucleotides (ASOs). α-Syn-HDO attenuated abnormal α-Syn expression and ameliorated dopaminergic neuron degeneration via BDNF upregulation by activation of CREB and inhibition of MeCP2. These findings demonstrated that inhibition of α-Syn by α-Syn-HDO protected against dopaminergic neuron degeneration via activation of BDNF transcription. Therefore, α-Syn-HDO may serve as a new therapeutic agent for PD. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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