Tissue Transglutaminase, Protein Cross-linking and Alzheimer's Disease: Review and Views

International Journal of Clinical and Experimental Pathology

James S Malter¹  Deng-Shun Wang¹  Dennis W Dickson¹ 

关键词: Tissue transglutaminase (tTG;    TG2);    Alzheimer's disease;    β-amyloid (Aβ);    tau;    α-synuclein;    neurofilament p;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

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, 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 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.

【 授权许可】

Unknown