PMID- 19233513
OWN - NLM
STAT- MEDLINE
DCOM- 20110314
LR  - 20151119
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 32
IP  - 1
DP  - 2011 Jan
TI  - Thiamine deficiency increases beta-secretase activity and accumulation of beta-amyloid 
      peptides.
PG  - 42-53
LID - 10.1016/j.neurobiolaging.2009.01.005 [doi]
AB  - Thiamine pyrophosphate (TPP) and the activities of thiamine-dependent enzymes are 
      reduced in Alzheimer's disease (AD) patients. In this study, we analyzed the 
      relationship between thiamine deficiency (TD) and amyloid precursor protein (APP) 
      processing in both cellular and animal models of TD. In SH-SY5Y neuroblastoma 
      cells overexpressing APP, TD promoted maturation of beta-site APP cleaving enzyme 1 
      (BACE1) and increased beta-secretase activity which resulted in elevated levels of 
      beta-amyloid (Abeta) as well as beta-secretase cleaved C-terminal fragment (beta-CTF). An 
      inhibitor of beta-secretase efficiently reduced TD-induced up-regulation of Abeta and 
      beta-CTF. Importantly, thiamine supplementation reversed the TD-induced alterations. 
      Furthermore, TD treatment caused a significant accumulation of reactive oxygen 
      species (ROS); antioxidants suppressed ROS production and maturation of BACE1, as 
      well as TD-induced Abeta accumulation. On the other hand, exogenous Abeta(1-40) 
      enhanced TD-induced production of ROS. A study on mice indicated that TD also 
      caused Abeta accumulation in the brain, which was reversed by thiamine 
      supplementation. Taken together, our study suggests that TD could enhance Abeta 
      generation by promoting beta-secretase activity, and the accumulation of Abeta 
      subsequently exacerbated TD-induced oxidative stress.
CI  - Copyright (c) 2009 Elsevier Inc. All rights reserved.
FAU - Zhang, Qipeng
AU  - Zhang Q
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 
      Shanghai, 200031, PR China.
FAU - Yang, Guang
AU  - Yang G
FAU - Li, Wenxia
AU  - Li W
FAU - Fan, Zhiqin
AU  - Fan Z
FAU - Sun, Anyang
AU  - Sun A
FAU - Luo, Jia
AU  - Luo J
FAU - Ke, Zun-Ji
AU  - Ke ZJ
LA  - eng
GR  - AA015407/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090223
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Antioxidants)
RN  - 0 (Chromans)
RN  - 0 (Peptide Fragments)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 5JB3029BJ7 (Pyrithiamine)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (Bace1 protein, mouse)
RN  - S18UL9710X (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid)
RN  - X66NSO3N35 (Thiamine)
SB  - IM
MH  - Amyloid Precursor Protein Secretases/*metabolism
MH  - Amyloid beta-Peptides/*metabolism/pharmacology
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Analysis of Variance
MH  - Animals
MH  - Antioxidants/therapeutic use
MH  - Aspartic Acid Endopeptidases/metabolism
MH  - Brain/*metabolism
MH  - Cell Death/physiology
MH  - Cell Line, Tumor
MH  - Chromans/therapeutic use
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroblastoma/pathology
MH  - Peptide Fragments/metabolism/pharmacology
MH  - Pyrithiamine/adverse effects
MH  - Reactive Oxygen Species/metabolism
MH  - Thiamine/administration & dosage
MH  - Thiamine Deficiency/drug therapy/etiology/*metabolism/*pathology
MH  - Time Factors
EDAT- 2009/02/24 09:00
MHDA- 2011/03/15 06:00
CRDT- 2009/02/24 09:00
PHST- 2008/08/12 00:00 [received]
PHST- 2008/12/28 00:00 [revised]
PHST- 2009/01/07 00:00 [accepted]
PHST- 2009/02/24 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2011/03/15 06:00 [medline]
AID - S0197-4580(09)00022-0 [pii]
AID - 10.1016/j.neurobiolaging.2009.01.005 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2011 Jan;32(1):42-53. doi: 10.1016/j.neurobiolaging.2009.01.005. 
      Epub 2009 Feb 23.