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PMID: 18855662 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease.

Current medicinal chemistry ·Vol. 15 ·No. 23 ·2008-00-00 ·Pages 2321-8

Gong CX, Iqbal K

Abstract

Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3beta (GSK-3beta), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.

MeSH Terms
Alzheimer Disease/genetics,metabolism,pathology,therapy Animals Humans Microtubules/metabolism Phosphorylation Protein Binding tau Proteins/genetics,metabolism
Chemicals
tau Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gong C-X
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA. cxgong@mail.csi.cuny.edu
Iqbal K
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Article Info
Journal
Current medicinal chemistry
Abbr.
Curr Med Chem
ISSN
0929-8673
DOI
10.2174/092986708785909111
Email
cxgong@mail.csi.cuny.edu
Published
2008-00-00
Pages
2321-8
Language
English
Region
United Arab Emirates
NLM ID
9440157
PMCID
PMC2656563
Subset
IM
Grants
NIA NIH HHS · R01 AG027429 · United States
NIA NIH HHS · R01 AG019158 · United States
NIA NIH HHS · AG019158 · United States
NIA NIH HHS · R01 AG027429-03 · United States
NIA NIH HHS · AG027429 · United States
External Links
PubMed source DOI: 10.2174/092986708785909111 PMC Full Text View journal details
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