The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons

Sook Wern Chua, Alberto Cornejo, Janet Van Eersel, Claire H. Stevens, Inmaculada Vaca, Mercedes Cueto, Michael Kassiou, Amadeus Gladbach, Alex Macmillan, Lev Lewis, Renee Whan, Lars M. Ittner

Resultado de la investigación: Article

10 Citas (Scopus)

Resumen

In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.

Idioma originalEnglish
Páginas (desde-hasta)743-751
Número de páginas9
PublicaciónACS Chemical Neuroscience
Volumen8
N.º4
DOI
EstadoPublished - 19 abr 2017

Huella dactilar

Polyphenols
Pathology
Neurons
Neurofibrillary Tangles
Agglomeration
Polyphenolic compounds
tau Proteins
Phosphorylation
Microtubule-Associated Proteins
Atomic Force Microscopy
Oligomers
Dimers
Transgenic Mice
Atomic force microscopy
Alzheimer Disease
Stabilization
Cells
Clinical Trials
altenusin
In Vitro Techniques

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Cognitive Neuroscience
  • Cell Biology

Citar esto

Chua, Sook Wern ; Cornejo, Alberto ; Van Eersel, Janet ; Stevens, Claire H. ; Vaca, Inmaculada ; Cueto, Mercedes ; Kassiou, Michael ; Gladbach, Amadeus ; Macmillan, Alex ; Lewis, Lev ; Whan, Renee ; Ittner, Lars M. / The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons. En: ACS Chemical Neuroscience. 2017 ; Vol. 8, N.º 4. pp. 743-751.
@article{a7cd783ae7d34e709b5de903cbce1850,
title = "The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons",
abstract = "In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.",
keywords = "Alzheimer's disease, antiaggregation, Microtubule associated protein tau",
author = "Chua, {Sook Wern} and Alberto Cornejo and {Van Eersel}, Janet and Stevens, {Claire H.} and Inmaculada Vaca and Mercedes Cueto and Michael Kassiou and Amadeus Gladbach and Alex Macmillan and Lev Lewis and Renee Whan and Ittner, {Lars M.}",
year = "2017",
month = "4",
day = "19",
doi = "10.1021/acschemneuro.6b00433",
language = "English",
volume = "8",
pages = "743--751",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "4",

}

Chua, SW, Cornejo, A, Van Eersel, J, Stevens, CH, Vaca, I, Cueto, M, Kassiou, M, Gladbach, A, Macmillan, A, Lewis, L, Whan, R & Ittner, LM 2017, 'The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons', ACS Chemical Neuroscience, vol. 8, n.º 4, pp. 743-751. https://doi.org/10.1021/acschemneuro.6b00433

The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons. / Chua, Sook Wern; Cornejo, Alberto; Van Eersel, Janet; Stevens, Claire H.; Vaca, Inmaculada; Cueto, Mercedes; Kassiou, Michael; Gladbach, Amadeus; Macmillan, Alex; Lewis, Lev; Whan, Renee; Ittner, Lars M.

En: ACS Chemical Neuroscience, Vol. 8, N.º 4, 19.04.2017, p. 743-751.

Resultado de la investigación: Article

TY - JOUR

T1 - The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons

AU - Chua, Sook Wern

AU - Cornejo, Alberto

AU - Van Eersel, Janet

AU - Stevens, Claire H.

AU - Vaca, Inmaculada

AU - Cueto, Mercedes

AU - Kassiou, Michael

AU - Gladbach, Amadeus

AU - Macmillan, Alex

AU - Lewis, Lev

AU - Whan, Renee

AU - Ittner, Lars M.

PY - 2017/4/19

Y1 - 2017/4/19

N2 - In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.

AB - In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.

KW - Alzheimer's disease

KW - antiaggregation

KW - Microtubule associated protein tau

UR - http://www.scopus.com/inward/record.url?scp=85018473985&partnerID=8YFLogxK

U2 - 10.1021/acschemneuro.6b00433

DO - 10.1021/acschemneuro.6b00433

M3 - Article

VL - 8

SP - 743

EP - 751

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 4

ER -