Role of Tau and Amyloid-beta in autophagy gene dysregulation through oxidative stress
Haghi, Mehrnaz ; Masoudi, Raheleh ; Ataellahi, Fatemeh ; Yousefi, Reza and Najibi, Seyed Morteza LU
(2025)
In Tissue and Cell
93.
p.1-12
- Abstract
BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by memory impairment and cognitive decline. Our previous research has demonstrated that pathological Tau and Amyloid-beta (Aβ) disrupt autophagy gene expression, independently. Other studies have shown that these pathological aggregates create a vicious cycle with oxidative stress.
METHODS: In the current research, the effect of Tau and Amyloid-beta was compared on behavioral function, autophagy gene dysfunction, and oxidative stress in the Drosophila model for AD. Thymoquinone (TQ), an antioxidant agent, was then tested to examine if it could ameliorate the adverse effects of Tau and Amyloid-beta. In addition, the impact of TQ on Tau... (More)
BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by memory impairment and cognitive decline. Our previous research has demonstrated that pathological Tau and Amyloid-beta (Aβ) disrupt autophagy gene expression, independently. Other studies have shown that these pathological aggregates create a vicious cycle with oxidative stress.
METHODS: In the current research, the effect of Tau and Amyloid-beta was compared on behavioral function, autophagy gene dysfunction, and oxidative stress in the Drosophila model for AD. Thymoquinone (TQ), an antioxidant agent, was then tested to examine if it could ameliorate the adverse effects of Tau and Amyloid-beta. In addition, the impact of TQ on Tau aggregation was investigated in vitro.
RESULTS: Our data showed that Tau and Amyloid-beta induced behavioral disability, autophagy gene dysregulation, and oxidative stress. TQ treatment significantly improved conditions in both types of transgenic flies, with a more profound alleviation in Tau transgenic flies, despite tau having a greater impact on autophagy gene dysregulation. Furthermore, TQ prevented the aggregation of Tau in vitro.
CONCLUSION: To sum up, Tau may exert its toxic effect on autophagy and behavioral dysfunctions significantly through oxidative stress while Amyloid-beta may confer its toxicity through multiple pathways, including oxidative stress. Moreover, since TQ ameliorates the adverse effect of tau and amyloid beta, it could be considered a promising approach for treating AD, probably in combination with other medications against Aβ or Tau.
(Less)
- author
- Haghi, Mehrnaz
; Masoudi, Raheleh
; Ataellahi, Fatemeh
; Yousefi, Reza
and Najibi, Seyed Morteza
LU
- organization
- publishing date
- 2025-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Oxidative Stress/drug effects, tau Proteins/metabolism, Animals, Autophagy/drug effects, Amyloid beta-Peptides/metabolism, Drosophila melanogaster/genetics, Animals, Genetically Modified, Alzheimer Disease/metabolism, Disease Models, Animal, Gene Expression Regulation/drug effects, Humans, Drosophila Proteins/metabolism
- in
- Tissue and Cell
- volume
- 93
- article number
- 102765
- pages
- 1 - 12
- publisher
- Elsevier
- external identifiers
-
- pmid:39923646
- scopus:85217095328
- ISSN
- 0040-8166
- DOI
- 10.1016/j.tice.2025.102765
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2025. Published by Elsevier Ltd.
- id
- dd1806d7-9e64-4ab3-a3b3-d3b8c77193f5
- date added to LUP
- 2025-03-19 00:11:34
- date last changed
- 2025-07-09 13:07:06
@article{dd1806d7-9e64-4ab3-a3b3-d3b8c77193f5,
abstract = {{<p>BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by memory impairment and cognitive decline. Our previous research has demonstrated that pathological Tau and Amyloid-beta (Aβ) disrupt autophagy gene expression, independently. Other studies have shown that these pathological aggregates create a vicious cycle with oxidative stress.</p><p>METHODS: In the current research, the effect of Tau and Amyloid-beta was compared on behavioral function, autophagy gene dysfunction, and oxidative stress in the Drosophila model for AD. Thymoquinone (TQ), an antioxidant agent, was then tested to examine if it could ameliorate the adverse effects of Tau and Amyloid-beta. In addition, the impact of TQ on Tau aggregation was investigated in vitro.</p><p>RESULTS: Our data showed that Tau and Amyloid-beta induced behavioral disability, autophagy gene dysregulation, and oxidative stress. TQ treatment significantly improved conditions in both types of transgenic flies, with a more profound alleviation in Tau transgenic flies, despite tau having a greater impact on autophagy gene dysregulation. Furthermore, TQ prevented the aggregation of Tau in vitro.</p><p>CONCLUSION: To sum up, Tau may exert its toxic effect on autophagy and behavioral dysfunctions significantly through oxidative stress while Amyloid-beta may confer its toxicity through multiple pathways, including oxidative stress. Moreover, since TQ ameliorates the adverse effect of tau and amyloid beta, it could be considered a promising approach for treating AD, probably in combination with other medications against Aβ or Tau.</p>}},
author = {{Haghi, Mehrnaz and Masoudi, Raheleh and Ataellahi, Fatemeh and Yousefi, Reza and Najibi, Seyed Morteza}},
issn = {{0040-8166}},
keywords = {{Oxidative Stress/drug effects; tau Proteins/metabolism; Animals; Autophagy/drug effects; Amyloid beta-Peptides/metabolism; Drosophila melanogaster/genetics; Animals, Genetically Modified; Alzheimer Disease/metabolism; Disease Models, Animal; Gene Expression Regulation/drug effects; Humans; Drosophila Proteins/metabolism}},
language = {{eng}},
pages = {{1--12}},
publisher = {{Elsevier}},
series = {{Tissue and Cell}},
title = {{Role of Tau and Amyloid-beta in autophagy gene dysregulation through oxidative stress}},
url = {{http://dx.doi.org/10.1016/j.tice.2025.102765}},
doi = {{10.1016/j.tice.2025.102765}},
volume = {{93}},
year = {{2025}},
}