Extracellular Hsp90α stimulates a unique innate gene profile in microglial cells with simultaneous activation of Nrf2 and protection from oxidative stress

Okusha, Yuka; Lang, Benjamin; Murshid, Ayesha; Borges, Thiago J.; Holton, Kristina M.; Clark-Matott, Joanne; Doshi, Sachin; Ikezu, Tsuneya; Calderwood, Stuart K.

doi:10.1007/s12192-022-01279-9

Cited by 4 publications

(1 citation statement)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is highly germane to AD as a large body of evidence indicates that HSP90 activation may decrease AD-like pathology developed by mouse models of this disease [ 81 , 85 ]. While the mechanism mediating this improvement remains to be established, in a recent work, Okusha and colleagues showed that one way by which Hsp90 may attempt to protect the brain from Aβ-induced damage is by activating Nrf2 [ 86 ]. Indeed, they showed that increasing the levels of Hsp90 led to higher Nrf2 phosphorylation at serine 40, which ultimately resulted in increased Nrf2 transcriptional activity.…”

Section: Nrf2 Heat Shock Proteins and Admentioning

confidence: 99%

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

et al. 2023

View full text Add to dashboard Cite

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 Aβ and tau reduces Nrf2 levels, decreasing the antioxidant response. The reduced Nrf2 levels contribute to the further accumulation of Aβ 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.

show abstract

Section: Nrf2 Heat Shock Proteins and Admentioning

confidence: 99%