Alzheimer's disease (AD) is a common neurodegenerative disorder that affects the elderly. One of the key features of AD is the accumulation of reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of the antioxidant response in cells. Under low ROS levels, Nrf2 is kept in the cytoplasm. However, an increase in ROS production leads to a translocation of Nrf2 into the nucleus, where it activates the transcription of several genes involved in the cells' antioxidant response. Additionally, Nrf2 activation increases autophagy function. However, in AD, the accumulation of A beta and tau reduces Nrf2 levels, decreasing the antioxidant response. The reduced Nrf2 levels contribute to the further accumulation of A beta and tau by impairing their autophagy-mediated turnover. In this review, we discuss the overwhelming evidence indicating that genetic or pharmacological activation of Nrf2 is as a potential approach to mitigate AD pathology.

The Role of the Transcription Factor Nrf2 in Alzheimer's Disease: Therapeutic Opportunities

De Plano, Laura Maria
Primo
;
Calabrese, Giovanna
Secondo
;
Rizzo, Maria Giovanna;Oddo, Salvatore
Penultimo
;
Caccamo, Antonella
Ultimo
2023-01-01

Abstract

Alzheimer's disease (AD) is a common neurodegenerative disorder that affects the elderly. One of the key features of AD is the accumulation of reactive oxygen species (ROS), which leads to an overall increase in oxidative damage. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of the antioxidant response in cells. Under low ROS levels, Nrf2 is kept in the cytoplasm. However, an increase in ROS production leads to a translocation of Nrf2 into the nucleus, where it activates the transcription of several genes involved in the cells' antioxidant response. Additionally, Nrf2 activation increases autophagy function. However, in AD, the accumulation of A beta and tau reduces Nrf2 levels, decreasing the antioxidant response. The reduced Nrf2 levels contribute to the further accumulation of A beta and tau by impairing their autophagy-mediated turnover. In this review, we discuss the overwhelming evidence indicating that genetic or pharmacological activation of Nrf2 is as a potential approach to mitigate AD pathology.
2023
File in questo prodotto:
File Dimensione Formato  
biomolecules-13-00549.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 827.78 kB
Formato Adobe PDF
827.78 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3259307
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 23
social impact