TY - JOUR
T1 - PHF-Core Tau as the Potential Initiating Event for Tau Pathology in Alzheimer’s Disease
AU - Luna-Viramontes, Nabil Itzi
AU - Campa-Córdoba, B. Berenice
AU - Ontiveros-Torres, Miguel Angel
AU - Harrington, Charles R
AU - Villanueva-Fierro, Ignacio
AU - Guadarrama-Ortíz, Parménides
AU - Garcés-Ramírez, Linda
AU - de la Cruz, Fidel
AU - Hernandes-Alejandro, Mario
AU - Martínez-Robles, Sandra
AU - González-Ballesteros, Erik
AU - Pacheco-Herrero, Mar
AU - Luna-Muñoz, José
N1 - FUNDING
This work was supported by Fondo Nacional de Ciencia, Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015- 3A2-127 to MP-H and 2018-2019-2A3-208 to JL-M and MP-H).
ACKNOWLEDGMENTS:
We want to express our gratitude to the following: Dr. P. Davies (Albert Einstein College of Medicine, Bronx, NY, United States) and Lester I. Binder† (North Western, Chicago, IL, United States) for the generous gifts of mAbs TG3 and Alz-50, and Tau-1, Tau-5, and Tau-7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; Samadhi Moreno-Campuzano for her technical assistance/support in the confocal microscopy unit of CIIDIR
Durango, Instituto Politécnico Nacional; Union Medical University Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with
Alzheimer’s disease and made our research possible. This work is dedicated to the memory of Professor Dr. José Raúl Mena López†
.
PY - 2020/9/10
Y1 - 2020/9/10
N2 - Worldwide, around 50 million people have dementia. Alzheimer’s disease (AD) is the most common type of dementia and one of the major causes of disability and dependency among the elderly worldwide. Clinically, AD is characterized by impaired memory accompanied by other deficiencies in the cognitive domain. Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) are histopathological lesions that define brains with AD. NFTs consist of abundant intracellular paired helical filaments (PHFs) whose main constituent is tau protein. Tau undergoes posttranslational changes including hyperphosphorylation and truncation, both of which favor conformational changes in the protein. The sequential pathological processing of tau is illustrated with the following specific markers: pT231, TG3, AT8, AT100, and Alz50. Two proteolysis sites for tau have been described—truncation at glutamate 391 and at aspartate 421—and which can be demonstrated by reactivity with the antibodies 423 and TauC-3, respectively. In this review, we describe the molecular changes in tau protein as pre-NFTs progress to extracellular NFTs and during which the formation of a minimal nucleus of the filament, as the PHF core, occurs. We also analyzed the PHF core as the initiator of PHFs and tau phosphorylation as a protective neuronal mechanism against the assembly of the PHF core.
AB - Worldwide, around 50 million people have dementia. Alzheimer’s disease (AD) is the most common type of dementia and one of the major causes of disability and dependency among the elderly worldwide. Clinically, AD is characterized by impaired memory accompanied by other deficiencies in the cognitive domain. Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) are histopathological lesions that define brains with AD. NFTs consist of abundant intracellular paired helical filaments (PHFs) whose main constituent is tau protein. Tau undergoes posttranslational changes including hyperphosphorylation and truncation, both of which favor conformational changes in the protein. The sequential pathological processing of tau is illustrated with the following specific markers: pT231, TG3, AT8, AT100, and Alz50. Two proteolysis sites for tau have been described—truncation at glutamate 391 and at aspartate 421—and which can be demonstrated by reactivity with the antibodies 423 and TauC-3, respectively. In this review, we describe the molecular changes in tau protein as pre-NFTs progress to extracellular NFTs and during which the formation of a minimal nucleus of the filament, as the PHF core, occurs. We also analyzed the PHF core as the initiator of PHFs and tau phosphorylation as a protective neuronal mechanism against the assembly of the PHF core.
KW - tau protein
KW - tau pathology
KW - PHF core
KW - Truncation
KW - phosphorylation
KW - conformational changes
KW - paired helical filament
KW - neurofibrillary tangles
KW - truncation
UR - http://www.scopus.com/inward/record.url?scp=85091531587&partnerID=8YFLogxK
U2 - 10.3389/fncel.2020.00247
DO - 10.3389/fncel.2020.00247
M3 - Article
C2 - 33132840
VL - 14
JO - Frontiers in cellular neuroscience
JF - Frontiers in cellular neuroscience
SN - 1662-5102
M1 - 247
ER -