Journal ArticleDOI
Role of the Keap1/Nrf2 pathway in neurodegenerative diseases.
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TLDR
Current research unequivocally demonstrates that the activation of the Nrf2 pathway is a promising novel strategy for the prevention and modification of neurodegenerative diseases.Abstract:
As the elderly population increases, a growing number of individuals suffer from age-associated neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Oxidative stress is considered to play a crucial role in the pathogenesis of age-related diseases. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is activated by oxidative stress and regulates the expression of a variety of antioxidant enzymes and proteins that exert cytoprotective effects against oxidative stress. Numerous studies have addressed the role of Nrf2 in age-related diseases, including neurodegenerative diseases, using animal or in vitro cell culture models. Here, we introduce the role of oxidative stress in the pathogenesis of neurodegenerative diseases and critically examine the recent findings concerning the role for Nrf2 in the amelioration of AD and PD. Nrf2 not only regulates antioxidant proteins but also regulates the genes associated with autophagy and nerve growth factor signaling. Current research unequivocally demonstrates that the activation of the Nrf2 pathway is a promising novel strategy for the prevention and modification of neurodegenerative diseases.read more
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Journal ArticleDOI
Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism
TL;DR: This review summarizes knowledge about Nrf2 and HO-1 across different phyla suggesting their conservative role as stress-protective and anti-aging factors.
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Nrf2-ARE pathway: An emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases.
TL;DR: The role of the nuclear factor E2-related factor 2 (Nrf2) as a potential target for the treatment of neurodegenerative diseases is addressed and deregulation of the Nrf2 pathway in different NDDs is reviewed.
Journal ArticleDOI
The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases.
TL;DR: It is suggested that the Keap1–Nrf2 system is a potential therapeutic target to combat cancer and NDD by designing and developing modulators (inhibitors/activators) for Nrf2 activation.
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Repurposing the NRF2 Activator Dimethyl Fumarate as Therapy Against Synucleinopathy in Parkinson's Disease.
Isabel Lastres-Becker,Ángel Juan García-Yagüe,Ángel Juan García-Yagüe,Robert H. Scannevin,María J. Casarejos,Sebastian Kügler,Alberto Rábano,Antonio Cuadrado,Antonio Cuadrado +8 more
TL;DR: These experiments provide a compelling rationale for targeting NRF2 with DMF as a therapeutic strategy to reinforce endogenous brain defense mechanisms against PD-associated synucleinopathy and are ready for clinical validation in PD.
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The role of Nrf2 signaling in counteracting neurodegenerative diseases.
TL;DR: Targeting Nrf2 signaling may provide a therapeutic option to delay onset, slow progression, and ameliorate symptoms of neurodegenerative disorders.
References
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Journal ArticleDOI
An nrf2/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements
Ken Itoh,Tomoki Chiba,Satoru Takahashi,Tetsuro Ishii,Kazuhiko Igarashi,Yasutake Katoh,Tatsuya Oyake,Norio Hayashi,Kimihiko Satoh,Ichiro Hatayama,Masayuki Yamamoto,Yo-ichi Nabeshima +11 more
TL;DR: It is demonstrated that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes and the nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.
Journal ArticleDOI
Neurodegenerative diseases and oxidative stress.
TL;DR: Oxidative stress has been implicated in the progression of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and different strategies, including novel metal–protein attenuating compounds aimed at a variety of targets have shown promise in clinical studies.
Journal ArticleDOI
Mechanisms underlying inflammation in neurodegeneration.
TL;DR: There is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators in neurodegenerative diseases.
Journal ArticleDOI
The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1
Masaaki Komatsu,Hirofumi Kurokawa,Satoshi Waguri,Keiko Taguchi,Akira Kobayashi,Yoshinobu Ichimura,Yoshinobu Ichimura,Yu-shin Sou,Yu-shin Sou,Izumi Ueno,Ayako Sakamoto,Kit I. Tong,Mihee Kim,Yasumasa Nishito,Shun-ichiro Iemura,Tohru Natsume,Takashi Ueno,Eiki Kominami,Hozumi Motohashi,Keiji Tanaka,Masayuki Yamamoto +20 more
TL;DR: The findings indicate that the pathological process associated with p62 accumulation results in hyperactivation of Nrf2 and delineates unexpected roles of selective autophagy in controlling the transcription of cellular defence enzyme genes.
Journal ArticleDOI
Oxidative stress in neurodegeneration: cause or consequence?
TL;DR: A review of the evidence for oxidative stress in neurodegeneration and how this relates to other cellular events can be found in this article, where a growing number of in vitro and in vivo models that emulate human disease pathology is aiding scientists in deciphering just where oxidative stress intersects with other cellular processes.
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