PMID- 21338582
OWN - NLM
STAT- MEDLINE
DCOM- 20120312
LR  - 20211020
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1386
DP  - 2011 Apr 22
TI  - A microRNA embedded AAV alpha-synuclein gene silencing vector for dopaminergic 
      neurons.
PG  - 15-24
LID - 10.1016/j.brainres.2011.02.041 [doi]
AB  - Alpha-synuclein (SNCA), an abundantly expressed presynaptic protein, is 
      implicated in Parkinson's disease (PD). Since over-expression of human SNCA 
      (hSNCA) leads to death of dopaminergic (DA) neurons in human, rodent and fly 
      brain, hSNCA gene silencing may reduce levels of toxic forms of SNCA and 
      ameliorate degeneration of DA neurons in PD. To begin to develop a gene therapy 
      for PD based on hSNCA gene silencing, two AAV gene silencing vectors were 
      designed, and tested for efficiency and specificity of silencing, as well as 
      toxicity in vitro. The same hSNCA silencing sequence (shRNA) was used in both 
      vectors, but in one vector, the shRNA was embedded in a microRNA backbone and 
      driven by a pol II promoter, and in the other the shRNA was not embedded in a 
      microRNA and was driven by a pol III promoter. Both vectors silenced hSNCA to the 
      same extent in 293T cells transfected with hSNCA. In DA PC12 cells, neither 
      vector decreased expression of rat SNCA, tyrosine hydroxylase (TH), dopamine 
      transporter (DAT) or the vesicular monoamine transporter (VMAT). However, the 
      mir30 embedded vector was significantly less toxic to both PC12 and SH-SY5Y 
      cells. Our in vitro data suggest that this miRNA-embedded silencing vector may be 
      ideal for chronic in vivo SNCA gene silencing in DA neurons.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Han, Ye
AU  - Han Y
AD  - Neurobiology Program, Department of Pediatrics, Children's Memorial Research 
      Center, Feinberg School of Medicine, Northwestern University,Chicago, IL 60614, 
      USA.
FAU - Khodr, Christina E
AU  - Khodr CE
FAU - Sapru, Mohan K
AU  - Sapru MK
FAU - Pedapati, Jyothi
AU  - Pedapati J
FAU - Bohn, Martha C
AU  - Bohn MC
LA  - eng
GR  - T32 NS041234/NS/NINDS NIH HHS/United States
GR  - NS054989/NS/NINDS NIH HHS/United States
GR  - R21 NS054989/NS/NINDS NIH HHS/United States
GR  - T32 NS041234-10/NS/NINDS NIH HHS/United States
GR  - R21 NS054989-01A1/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110219
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (MIRN30b microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (SNCA protein, human)
RN  - 0 (alpha-Synuclein)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Dependovirus/*genetics
MH  - Dopamine/*metabolism
MH  - Gene Silencing/*physiology
MH  - Genetic Vectors/physiology/*toxicity
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - MicroRNAs/genetics/*toxicity
MH  - Neurons/*metabolism/pathology
MH  - PC12 Cells
MH  - Parkinson Disease/genetics/pathology/therapy
MH  - Plasmids/genetics
MH  - Rats
MH  - alpha-Synuclein/*antagonists & inhibitors/genetics
PMC - PMC3076891
MID - NIHMS282876
EDAT- 2011/02/23 06:00
MHDA- 2012/03/13 06:00
PMCR- 2012/04/22
CRDT- 2011/02/23 06:00
PHST- 2010/11/11 00:00 [received]
PHST- 2011/01/10 00:00 [revised]
PHST- 2011/02/14 00:00 [accepted]
PHST- 2011/02/23 06:00 [entrez]
PHST- 2011/02/23 06:00 [pubmed]
PHST- 2012/03/13 06:00 [medline]
PHST- 2012/04/22 00:00 [pmc-release]
AID - S0006-8993(11)00368-4 [pii]
AID - 10.1016/j.brainres.2011.02.041 [doi]
PST - ppublish
SO  - Brain Res. 2011 Apr 22;1386:15-24. doi: 10.1016/j.brainres.2011.02.041. Epub 2011 
      Feb 19.