Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration?

Abstract

Although the trigger for the neurodegenerative disease process is unknown, the relevance of aging stands out as a major risk for the development of neurodegeneration. In this review, we highlighted the relationship between the different cellular mechanisms that occur as a consequence of aging and transcription factor nuclear factor erythroid-2-related factor 2 (NRF2) and the connection with the TAU protein. We focused on the relevance of NRF2 in the main processes involved in neurodegeneration and associated with aging, such as genomic instability, protein degradation systems (proteasomes/autophagy), cellular senescence, and stem cell exhaustion, as well as inflammation. We also analyzed the effect of aging on TAU protein levels and its aggregation and spread process. Finally, we investigated the interconnection between NRF2 and TAU and the relevance of alterations in the NRF2 signaling pathway in both primary and secondary tauopathies. All these points highlight NRF2 as a possible therapeutic target for tauopathies.

Αnti-prion effects of anthocyanins

“…Consequently, it was tested whether the observed anti-oxidant effects of Oenin and Myrtillin in N2a22L cells also depended on Keap1-Nrf2 induction. Indeed, both ACN compounds managed to trigger the expression of key Nrf2 antioxidant target genes, GCLM and HMOX1 [ 77 ]. Interestingly, Myrtillin not only presented a more profound effect in GCLM and HMOX1 levels, but also upregulated the expression of Nrf2 ( NFE2L2 ) ( Fig.…”

Demethylcalabaxanthone from Garcinia mangostana Exerts Antioxidant Effects through the Activation of the Nrf2 Pathway as Assessed via Molecular Docking and Biological Evaluation

“…The possible involvement of the transcriptional factor Nrf2 in the cytoprotective effect of 1 and 4 was evaluated. Moreover, considering the interconnection between the Nrf2 pathway and TAU [37], the total amount of phosphorylated Nrf2 in the nucleus of HEK239-tau was determined with Western blot, using β-actin as the control.…”