+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Role of the Keap1/Nrf2 pathway in neurodegenerative diseases



Role of the Keap1/Nrf2 pathway in neurodegenerative diseases



Pathology International 65(5): 210-219



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058791100

Download citation: RISBibTeXText

PMID: 25707882

DOI: 10.1111/pin.12261


Related references

The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases. Biophysical Reviews 9(1): 41-56, 2017

Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis 30(9): 1571-1580, 2009

The cytoprotective role of the Keap1-Nrf2 pathway. Archives of Toxicology 85(4): 241-272, 2011

Role of the Keap1-Nrf2 pathway in cancer. Advances in Cancer Research 122: 281-320, 2015

Physical and functional interaction of sequestosome 1 with Keap1 regulates the Keap1-Nrf2 cell defense pathway. Journal of Biological Chemistry 285(22): 16782-8, 2010

The role of the Keap1/Nrf2 pathway in the cellular response to methylmercury. Oxidative Medicine and Cellular Longevity 2013: 848279, 2014

The role of the Nrf2/Keap1 pathway in obesity and metabolic syndrome. Reviews in Endocrine and Metabolic Disorders 16(1): 35-45, 2015

The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes and Development 27(20): 2179-2191, 2013

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma. Head and Neck 40(6): 1271-1278, 2018

Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma. Oncotarget 8(7): 11187-11198, 2017

The emerging role of redox-sensitive Nrf2-Keap1 pathway in diabetes. Pharmacological Research 91: 104-114, 2015

The Nrf2-Keap1 defence pathway: role in protection against drug-induced toxicity. Toxicology 246(1): 24-33, 2007

The Nrf2-Keap1-ARE signaling pathway: The regulation and dual function of Nrf2 in cancer. Antioxidants and Redox Signaling 13(11): 1623-1626, 2011

Tethering of Nrf2 to Keap1 prevents Nrf2 degradation by the ubiquitin proteasome pathway. Free Radical Biology & Medicine 33(Supplement 2): S350-S351, 2002

Marburgvirus hijacks nrf2-dependent pathway by targeting nrf2-negative regulator keap1. Cell Reports 6(6): 1026-1036, 2015