PMID- 23377801
OWN - NLM
STAT- MEDLINE
DCOM- 20130614
LR  - 20150407
IS  - 1128-3602 (Print)
IS  - 1128-3602 (Linking)
VI  - 17
IP  - 2
DP  - 2013 Jan
TI  - The association between lysosomal protein glucocerebrosidase and Parkinson's 
      disease.
PG  - 143-51
LID - 2926 [pii]
AB  - BACKGROUND: In recent years, mutations in glucocerebrosidase gene (GBA), which 
      encodes the lysosomal enzyme glucocerebrosidase (GCase) deficient in Gaucher 
      disease (GD), were found to be the most widespread genetic for the development of 
      Parkinson disease. AIM: In this work, we investigated the possibility of a 
      biological linkage between GCase and alpha-synuclein. MATERIALS AND METHODS: 
      siRNA was used to knockdown the GBA, then the related proteins such as 
      alpha-synuclein were detected, additionally, the mutations of GBA were also 
      detected. We also provide evidence that a mouse model of Gaucher disease 
      (GBAD409H/D409H) to detect the gene types of GBA. RESULTS: The results showed 
      functional knockdown (KD) of GBA in neuroblastoma cells culture causes a 
      significant accumulation of alpha-synuclein and alpha-synuclein-mediated 
      neurotoxicity. Furthermore, KD of GBA in rat primary neurons expressing the A53T 
      mutation of alpha-synuclein, decreases cell viability. In addition, we observed 
      that overexpression of several GBA mutants (N370S, L444P, D409H, D409V) 
      significantly raised human alpha-syn levels of vector control. Glucosylceramide 
      (GlcCer), the GCase substrate, influenced formation of purified a-syn by 
      stabilizing soluble oligomeric intermediates. We also provide evidence that a 
      mouse model of Gaucher disease (GBAD409H/D409H) exhibited alpha-syn aggregates in 
      substantia nigra, cortex and hippocampus regions. ELISA analysis showed a 
      significant rise in membrane-associated alpha-syn and western blot analysis showed 
      that two forms of alpha-syn oligomers were present in brain homogenates from the 
      hippocampus D409H mice. CONCLUSIONS: These studies support the contention that 
      both WT and mutant GBA can cause Parkinson disease-like alpha-synuclein 
      pathology.
FAU - Kong, B
AU  - Kong B
AD  - Department of Neurosurgery, Chengdu Military General Hospital, Chengdu, Sichuan, 
      China. gujianwen5000@gmail.com  
FAU - Yang, T
AU  - Yang T
FAU - Gu, J W
AU  - Gu JW
FAU - Kuang, Y Q
AU  - Kuang YQ
FAU - Cheng, L
AU  - Cheng L
FAU - Yang, W T
AU  - Yang WT
FAU - Yang, X K
AU  - Yang XK
FAU - Xia, X
AU  - Xia X
FAU - Cheng, J M
AU  - Cheng JM
FAU - Ma, Y
AU  - Ma Y
FAU - Zhang, J H
AU  - Zhang JH
FAU - Yu, S X
AU  - Yu SX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Proteins)
RN  - 0 (alpha-Synuclein)
RN  - 0 (lysosomal proteins)
RN  - EC 3.2.1.45 (Glucosylceramidase)
SB  - IM
RIN - Eur Rev Med Pharmacol Sci. 2015;19(2):179. PMID: 25683925
MH  - Animals
MH  - Brain Chemistry
MH  - Cell Line, Tumor
MH  - Female
MH  - Glucosylceramidase/*physiology
MH  - Humans
MH  - Mice
MH  - Parkinson Disease/enzymology/*etiology
MH  - Proteins/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - alpha-Synuclein/analysis/physiology
EDAT- 2013/02/05 06:00
MHDA- 2013/06/15 06:00
CRDT- 2013/02/05 06:00
PHST- 2013/02/05 06:00 [entrez]
PHST- 2013/02/05 06:00 [pubmed]
PHST- 2013/06/15 06:00 [medline]
AID - 2926 [pii]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2013 Jan;17(2):143-51.