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Wang DS, Dickson DW, Malter JS. Tissue transglutaminase, protein cross-linking and Alzheimer's disease: review and views. Int J Clin Exp Pathol. 2008;1(1):5-18
Wang, D. S., Dickson, D. W., & Malter, J. S. (2008). Tissue transglutaminase, protein cross-linking and Alzheimer's disease: review and views. International journal of clinical and experimental pathology, 1(1), 5-18.
Wang, Deng-Shun, et al. "Tissue transglutaminase, protein cross-linking and Alzheimer's disease: review and views." International journal of clinical and experimental pathology vol. 1,1 (2008): 5-18.
Wang DS, Dickson DW, Malter JS. Tissue transglutaminase, protein cross-linking and Alzheimer's disease: review and views. Int J Clin Exp Pathol. 2008 Jan 01;1(1):5-18. PMID: 18784819; PMCID: PMC2480529.
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Int J Clin Exp Pathol. 2008 Jan 01;1(1):5-18.

Tissue transglutaminase, protein cross-linking and Alzheimer's disease: review and views.

International journal of clinical and experimental pathology

Deng-Shun Wang, Dennis W Dickson, James S Malter

Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. [email protected]

PMID: 18784819 PMCID: PMC2480529

Abstract

Extensive protein cross-linking and aggregation are some of the most common molecular events in the pathogenesis of Alzheimer's disease (AD). Both beta-amyloid (Abeta) plaques and neurofibrillary tangles, 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 indicates that tissue transglutaminase (tTG), which catalyzes the cross-linking of a wide spectrum of proteins including Abeta, tau, alpha-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 Abeta, tau, alpha-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.

Keywords: Alzheimer's disease; Tissue transglutaminase (tTG, TG2); neurofilament proteins; protein cross-linking; tau; α-synuclein; β-amyloid (Aβ)

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