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Targeting Transcription Factor Nrf2 in Neurodegenerative Diseases

Paris-Redox-2021-Speaker Antonio-CuadradoProf. Antonio Cuadrado from Universidad Autonoma de Madrid, Spain will give a presentation entitled "Targeting Transcription Factor Nrf2 in Neurodegenerative Diseases" during the congress.

For the past years Prof. Cuadrado's main lane of research has been the validation of transcription factor Nrf2, master regulator of cellular homeostasis.

Prof. Cuadrado affirms that there is an urgent need to find a neuroprotective therapy for Alzheimer’s disease. They are studying the relevance of homeostatic deviations that result from loss of activity of transcription factor Nrf2, a crucial regulator of multiple stress responses. We have generated a mouse model that combines amyloidopathy and tauopathy with either wild type (AT-Nrf2-WT) or Nrf2 deficiency (AT-Nrf2-KO). AT-Nrf2-KO mice exhibit exacerbated deficits in spatial learning and memory and increased markers of proteinopathy, oxidative stress and neuroinflammation compared to AT-Nrf2-WT-mice. The Nrf2 activator dimethyl fumarate (DMF), which is the only approved drug targeting Nrf2, and is being used for the treatment of remitting relapsing multiple sclerosis reduced glial and inflammatory markers and improved cognition and motor complications in the ATNrf2WT mice. We are also analyzing redox and inflammatory biomarkers in blood of AD patients. We have analyzed the expression of 168 genes related to oxidative stress and inflammation in peripheral blood in a cohort of 40 non-demented controls vs. 40 matched early ADs. We found a positive correlation between several Nrf2 regulated and several NfκB regulated genes. This study demonstrates the relevance of normal homeostatic responses that decline with ageing, such as Nrf2 activity, in the protection and biomarker monitoring of AD.

 

Paris Redox 2021 Congress
October 13-15, 2021 - Paris, France & Online
www.isanh.net

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