PMID- 16460685
OWN - NLM
STAT- MEDLINE
DCOM- 20060425
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 341
IP  - 4
DP  - 2006 Mar 24
TI  - Down-regulation of alpha-synuclein expression can rescue dopaminergic cells from 
      cell death in the substantia nigra of Parkinson's disease rat model.
PG  - 1088-95
AB  - Fibrillization and aggregation of alpha-synuclein may play a critical role in 
      neurodegenerative diseases like Parkinson's diseases. Adeno-associated virus 
      (AAV) vector delivery of an alpha-synuclein ribozyme was tested for its silencing 
      effect on degenerating nigrostriatal neurons in the MPP(+) model of Parkinson's 
      disease. We designed alpha-synuclein ribozyme against human alpha-synuclein gene 
      expression and constructed alpha-synuclein ribozymes-carrying rAAV vector 
      (designated rAAV-SynRz). Co-transfection of rAAV-SynRz and rAAV-alpha-synuclein 
      into HEK293 cells resulted in down-regulation of alpha-synuclein protein 
      expression in vitro. Then, rAAV-SynRz was injected into the substantia nigra (SN) 
      of MPP(+)-treated rats. Cell counts of TH-positive neurons in the SN revealed 
      that rAAV-SynRz significantly protected TH-positive cells against apoptotic 
      death, compared with those of rAAV-EGFP or no rAAV injected rats. Our results 
      indicate that the use of rAAV-SynRz allowed the survival of higher number of 
      TH-positive neurons in SN in the MPP(+) model. Down-regulation of alpha-synuclein 
      expression could be potentially a suitable target for gene therapy of Parkinson's 
      disease.
FAU - Hayashita-Kinoh, Hiromi
AU  - Hayashita-Kinoh H
AD  - Research Institute for Diseases of Old Age, Juntendo University, Tokyo, Japan.
FAU - Yamada, Masanori
AU  - Yamada M
FAU - Yokota, Takanori
AU  - Yokota T
FAU - Mizuno, Yoshikuni
AU  - Mizuno Y
FAU - Mochizuki, Hideki
AU  - Mochizuki H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060125
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Pyridinium Compounds)
RN  - 0 (RNA, Catalytic)
RN  - 0 (alpha-Synuclein)
RN  - 0 (hammerhead ribozyme)
RN  - 694-56-4 (1-methylpyridinium)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Base Sequence
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Dopamine/*physiology
MH  - *Down-Regulation
MH  - Gene Expression Regulation
MH  - Humans
MH  - Male
MH  - Mice
MH  - Neurons/*physiology
MH  - Parkinson Disease, Secondary/chemically induced/pathology/*physiopathology
MH  - Pyridinium Compounds
MH  - RNA, Catalytic
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substantia Nigra/drug effects/*pathology
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - alpha-Synuclein/*biosynthesis/genetics
EDAT- 2006/02/08 09:00
MHDA- 2006/04/28 09:00
CRDT- 2006/02/08 09:00
PHST- 2006/01/05 00:00 [received]
PHST- 2006/01/10 00:00 [accepted]
PHST- 2006/02/08 09:00 [pubmed]
PHST- 2006/04/28 09:00 [medline]
PHST- 2006/02/08 09:00 [entrez]
AID - S0006-291X(06)00105-7 [pii]
AID - 10.1016/j.bbrc.2006.01.057 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2006 Mar 24;341(4):1088-95. doi: 
      10.1016/j.bbrc.2006.01.057. Epub 2006 Jan 25.