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

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...

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Published inFrontiers in neuroscience Vol. 9; p. 33
Main Authors Flores-Rodríguez, Paola, Ontiveros-Torres, Miguel A, Cárdenas-Aguayo, María C, Luna-Arias, Juan P, Meraz-Ríos, Marco A, Viramontes-Pintos, Amparo, Harrington, Charles R, Wischik, Claude M, Mena, Raúl, Florán-Garduño, Benjamin, Luna-Muñoz, José
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 11.02.2015
Frontiers Media S.A
Subjects
Alzheimer Disease
Alzheimer's disease
Amino acids
Apoptosis
Brain
C-Terminus
Epitopes
Filaments
Immunoglobulins
Immunohistochemistry
Kinases
Laboratories
Neurodegenerative diseases
Neurofibrillary Tangles
Neuroprotection
Neurotoxicity
Phosphorylation
Proteins
Psychiatry
Tau oligomers
Tau protein
Truncation
Mexico
PHFs
neurotoxicity
neurofibrillary tangles
tau oligomers
Alzheimer's disease
tau protein
truncation
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Summary: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.
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Edited by: Giuseppe Pignataro, Federico II University of Naples, Italy
Reviewed by: Jason Eriksen, University of Houston, USA; Anna Pannaccione, University of Naples Federico II, Italy
This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience.
This article is dedicated to our colleague and friend, Raúl Mena, who sadly passed away on June 11th, 2014.
These authors have contributed equally to this work.
ISSN:1662-4548
1662-453X
1662-453X
DOI:10.3389/fnins.2015.00033