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PMID: 18174027 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease.

FEBS letters ·Vol. 582 ·No. 2 ·2008-01-23 ·Pages 359-64

Liu Y, Liu F, Iqbal K, Grundke-Iqbal I, Gong CX

Abstract

Brain glucose uptake/metabolism is impaired in Alzheimer disease (AD). Here, we report that levels of the two major brain glucose transporters (GLUT1 and GLUT3) responsible for glucose uptake into neurons were decreased in AD brain. This decrease correlated to the decrease in O-GlcNAcylation, to the hyperphosphorylation of tau, and to the density of neurofibrillary tangles in human brains. We also found down-regulation of hypoxia-inducible factor 1, a major regulator of GLUT1 and GLUT3, in AD brain. These studies provide a possible mechanism by which GLUT1 and GLUT3 deficiency could cause impaired brain glucose uptake/metabolism and contribute to neurodegeneration via down-regulation of O-GlcNAcylation and hyperphosphorylation of tau in AD.

MeSH Terms
Acylation Alzheimer Disease/metabolism Astrocytes/metabolism Brain/metabolism Glucose Transporter Type 1/metabolism Glucose Transporter Type 2/metabolism Humans Phosphorylation tau Proteins/metabolism
Chemicals
Glucose Transporter Type 1 Glucose Transporter Type 2 tau Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Liu Ying
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
Liu Fei
Iqbal Khalid
Grundke-Iqbal Inge
Gong Cheng-Xin
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Article Info
Journal
FEBS letters
Abbr.
FEBS Lett
ISSN
0014-5793
DOI
10.1016/j.febslet.2007.12.035
Published
2008-01-23
Epub
2008-00-02
Pages
359-64
Language
English
Region
England
NLM ID
0155157
PMCID
PMC2247364
Subset
IM
Grants
NIA NIH HHS · R01 AG027429-02 · United States
NIA NIH HHS · R01 AG027429 · United States
NIA NIH HHS · AG 027429 · United States
NIA NIH HHS · P30 AG019610 · United States
NIA NIH HHS · P30 AG 19610 · United States
External Links
PubMed source DOI: 10.1016/j.febslet.2007.12.035 PMC Full Text View journal details
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