Research toward the development of a novel treatment for Parkinson disease by a moderate gene silencing with RNA interference.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390226
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: HOHJOH HIROHIKO 独立行政法人国立精神・神経医療研究センター, 神経研究所神経薬理研究部, 室長 (60238722)
• Co-Investigator(Kenkyū-buntansha): NAGAI Yoshitaka 独立行政法人国立精神, 神経医療研究センター・疾病研究第4部, 室長 (60335354)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: RNAi / パーキンソン病 / α-シヌクレイン / 多重重複変異 / ショウジョウバエ

Outline of Final Research Achievements

The alpha-synuclein (SNCA) gene is a responsible gene for Parkinson’s disease (PD); and not only nucleotide variations but also overexpression of SNCA appears to be involved in PD. A specific inhibition against mutant SNCA genes carrying nucleotide variations may be feasible by an allele-specific RNAi; however, there is no method for restoring the SNCA overexpression to a normal level. In this study we showed that an atypical RNAi using siRNAs that confer a moderate level of gene silencing was capable of controlling overexpressed SNCA genes to return to a normal level; named ‘expression-control RNAi’ (ExCont-RNAi). To further assess its therapeutic effects, PD-model flies that carried the human SNCA gene underwent an ExCont-RNAi treatment. The treated PD-flies demonstrated a significant improvement in their motor function. Our current findings suggested that ExCont-RNAi might be capable of becoming a novel therapeutic procedure for PD with the SNCA overexpression.

Free Research Field

分子生命科学