| RRC ID |
60828
|
| 著者 |
Uehara T, Choong CJ, Nakamori M, Hayakawa H, Nishiyama K, Kasahara Y, Baba K, Nagata T, Yokota T, Tsuda H, Obika S, Mochizuki H.
|
| タイトル |
Amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides targeting α-synuclein as a novel therapy for Parkinson's disease.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. A characteristic pathological feature of PD is cytoplasmic accumulation of α-synuclein (SNCA) protein. Multiplication of the SNCA gene in familial PD and pathological accumulation of SNCA protein during progression of sporadic PD suggest that increased SNCA protein levels increase the risk of PD. Thus, reducing SNCA expression levels could delay PD onset or modify the disease course. For efficient knock down, we designed and synthesized an amido-bridged nucleic acids (AmNA)-modified antisense oligonucleotide (ASO) that targeted SNCA with improved stability and cellular uptake in vivo. AmNA-ASO efficiently downregulated SNCA at both the mRNA and protein level in vitro and in vivo. Notably, AmNA-ASO was efficiently delivered into the mouse brain by intracerebroventricular injection without the aid of additional chemicals. Furthermore, administration of AmNA-ASO ameliorated neurological defects in PD model mice expressing human wild type SNCA. Taken together, these findings suggest that AmNA-ASO is a promising therapeutic strategy for SNCA-associated pathology in PD.
|
| 巻・号 |
9(1)
|
| ページ |
7567
|
| 公開日 |
2019-5-21
|
| DOI |
10.1038/s41598-019-43772-9
|
| PII |
10.1038/s41598-019-43772-9
|
| PMID |
31110191
|
| PMC |
PMC6527855
|
| MeSH |
Animals
HEK293 Cells
Humans
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Oligonucleotides / genetics
Parkinson Disease / therapy*
RNA, Antisense / genetics*
RNA, Antisense / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNAi Therapeutics / methods*
alpha-Synuclein / genetics*
alpha-Synuclein / metabolism
|
| IF |
4.011
|
| 引用数 |
4
|
| リソース情報 |
| 実験動物マウス |
RBRC02830 |
