REVIEW ARTICLE

Nrf2-Mediated Signaling as a Therapeutic Target in Alzheimer’s Disease

The Open Neurology Journal 21 June 2024 REVIEW ARTICLE DOI: 10.2174/011874205X319474240611070113

Abstract

Nrf2 is a major transcriptional factor that controls gene expression in normal health and pathological conditions. It regulates and controls the manifestation of various major elements of oxidative stress, neuro-inflammation, autophagy, and mitochondrial bioenergetics in the centre and periphery. Besides, Nrf2 activity is also controlled at various stages, such as protein degradation, transcription, and post-translation. Growing evidence suggests changes in the levels of Nrf2 in degenerative disorders, such as Alzheimer's disease (AD). AD is characterised by elevated oxidative stress, neuro-inflammation, synaptic dysfunction, and proteinopathies, which lead to the progressive loss of memory. A decrease in the expression of Nrf2 and its downstream target genes was identified in AD. Recent studies have shown that Nrf2 interferes with various main pathogenic processes in AD, including amyloid and tau pathologies. The current review focuses on brief in the regulation of Nrf2 and the association of Nrf2 with AD, along with the currently available Nrf2 activators.

Keywords: Nrf2, Alzheimer’s disease, Keap1, Reactive oxygen species, Amyloid, DNA.
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