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| IJCEP Copyright © 2007-All rights reserved. |
| International Journal of Clinical and Experimental Pathology |
Int J Clin Exp Pathol 1(1):5-18;2008
Review Article
Tissue Transglutaminase, Protein Cross-linking and Alzheimer’s disease:
Review and Views
Deng-Shun Wang, Dennis W. Dickson and James S. Malter
Department of Pathology and Laboratory Medicine, Waisman Center for Developmental Disability, University of Wisconsin School of
Medicine and Public Health, Madison, WI 53705 and Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL
32224
Received 1 July 2007; accepted with revision 28 July 2007; available online 1 January 2008
Abstract: Extensive protein cross-linking and aggregation are some of the most common molecular events in the pathogenesis of
Alzheimer’s disease (AD). Both β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT), which are extracellular and intracellular
proteinaceous aggregates, respectively, contribute to neuronal death and progressive cognitive decline. Although protein cross-linking
has been recognized and extensively studied for many years, the underlying mechanisms are largely unknown. Recent data indicate that
tissue transglutaminase (tTG), which catalyzes the cross-linking of a wide spectrum of proteins including Aβ, tau, α-synuclein and
neurofilament proteins, may be involved in protein aggregation in AD. Many AD risk factors, such as trauma, inflammation, ischemia and
stress, up-regulate tTG protein and activity levels. In this review, we summarize the evidence that tTG plays a role in AD, especially in
cross-linking of Aβ, tau, α-synuclein and neurofilament proteins. An experimentally testable hypothesis is that tTG may play a central role
in AD pathogenesis and that it provides a conceptual link between sporadic and familial AD through a shared pathogenic pathway.
(IJCEP707001).
Key Words: Tissue transglutaminase (tTG, tG2), Alzheimer’s disease, β-amyloid (Aβ), tau, α-synuclein, neurofilament proteins, protein
cross-linking.
Full Text PDF
Address all correspondences to: Deng-Shun Wang, MD, PhD, Department of Pathology and Laboratory Medicine, University of
Wisconsin School of Medicine, 1500 Highland Ave, Waisman Center, Rm T508, Madison, WI 53705, USA. Tel: (608) 262- 9825, Email:
dwang6@wisc.edu.
Review Article
Tissue Transglutaminase, Protein Cross-linking and Alzheimer’s disease:
Review and Views
Deng-Shun Wang, Dennis W. Dickson and James S. Malter
Department of Pathology and Laboratory Medicine, Waisman Center for Developmental Disability, University of Wisconsin School of
Medicine and Public Health, Madison, WI 53705 and Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL
32224
Received 1 July 2007; accepted with revision 28 July 2007; available online 1 January 2008
Abstract: Extensive protein cross-linking and aggregation are some of the most common molecular events in the pathogenesis of
Alzheimer’s disease (AD). Both β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT), which are extracellular and intracellular
proteinaceous aggregates, respectively, contribute to neuronal death and progressive cognitive decline. Although protein cross-linking
has been recognized and extensively studied for many years, the underlying mechanisms are largely unknown. Recent data indicate that
tissue transglutaminase (tTG), which catalyzes the cross-linking of a wide spectrum of proteins including Aβ, tau, α-synuclein and
neurofilament proteins, may be involved in protein aggregation in AD. Many AD risk factors, such as trauma, inflammation, ischemia and
stress, up-regulate tTG protein and activity levels. In this review, we summarize the evidence that tTG plays a role in AD, especially in
cross-linking of Aβ, tau, α-synuclein and neurofilament proteins. An experimentally testable hypothesis is that tTG may play a central role
in AD pathogenesis and that it provides a conceptual link between sporadic and familial AD through a shared pathogenic pathway.
(IJCEP707001).
Key Words: Tissue transglutaminase (tTG, tG2), Alzheimer’s disease, β-amyloid (Aβ), tau, α-synuclein, neurofilament proteins, protein
cross-linking.
Full Text PDF
Address all correspondences to: Deng-Shun Wang, MD, PhD, Department of Pathology and Laboratory Medicine, University of
Wisconsin School of Medicine, 1500 Highland Ave, Waisman Center, Rm T508, Madison, WI 53705, USA. Tel: (608) 262- 9825, Email:
dwang6@wisc.edu.