The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease

Paola Flores-Rodríguez, Miguel A Ontiveros-Torres, María C Cárdenas-Aguayo, Juan P Luna-Arias, Marco A Meraz-Ríos, Amparo Viramontes-Pintos, Charles R Harrington, Claude M Wischik, Raúl Mena, Benjamin Florán-Garduño, José Luna-Muñoz

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Abstract

We previously demonstrated that, in the early stages of tau processing in Alzheimer's disease, the N-terminal part of the molecule undergoes a characteristic cascade of phosphorylation and progressive misfolding of the proteins resulting in a structural conformation detected by Alz-50. In this immunohistochemical study of AD brain tissue, we have found that C-terminal truncation of tau at Asp-421 was an early event in tau aggregation and analyzed the relationship between phospho-dependent tau epitopes located at the C-terminus with truncation at Glu-391. The aim of this study was to determine whether C-terminal truncation may trigger events leading to the assembly of insoluble PHFs from soluble tau aggregates present in pre-tangle cells. Our findings suggest that there is a complex interaction between phosphorylated and truncated tau species. A model is presented here in which truncated tau protein represents an early neurotoxic species while phosphorylated tau species may provide a neuroprotective role in Alzheimer's disease.

Original languageEnglish
Article number33
Number of pages10
JournalFrontiers in Neuroscience
Volume9
DOIs
Publication statusPublished - 11 Feb 2015

Keywords

  • tau protein
  • truncation
  • neurotoxicity
  • neurofibrillary tangles
  • PHFs
  • tau oligomers
  • Alzheimer's disease

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    Flores-Rodríguez, P., Ontiveros-Torres, M. A., Cárdenas-Aguayo, M. C., Luna-Arias, J. P., Meraz-Ríos, M. A., Viramontes-Pintos, A., Harrington, C. R., Wischik, C. M., Mena, R., Florán-Garduño, B., & Luna-Muñoz, J. (2015). The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease. Frontiers in Neuroscience, 9, [33]. https://doi.org/10.3389/fnins.2015.00033