Conformational changes and cleavage; are these responsible for the tau aggregation in Alzheimer''s disease?

• Published in: Future Neurology Vol. 4; no. 1; pp. 39 - 53
• Main Authors: MondragóóN-RodrííGuez, Siddhartha, Basurto-Islas, Gustavo, Binder, Lester I, GarcííA-Sierra, Francisco
• Format: Book Review Journal Article
• Language: English
• Published: London Future Medicine Ltd 01.01.2009
• ISSN: 1479-6708; 1748-6971
• DOI: 10.2217/14796708.4.1.39

In the past, post-translational modifications of tau protein, such as phosphorylation, cleavage and conformational changes, have long been implicated in the pathogenesis of Alzheimer''s disease. Unfortunately, the accurate role and relationship between these pathological modifications during tau aggregation remains under extensive study. We had proposed a chronological model of tau pathological processing during Alzheimer´´s disease, in which phosphorylation and cleavage could lead to conformational changes causing aggregation and therefore, cell toxicity. We discuss this issue and review in vitro and in situ evidence that supports the relevance of tau modifications that cause its pathological conformations and toxic aggregation. Thus, we offer a brief discussion regarding conformational change and cleavage as future clinical targets.