The crosstalk between oxidative stress and DNA damage induces neural stem cell senescence by HO-1/PARP1 non-canonical pathway.

Neural stem cells play a crucial role in maintaining brain homeostasis. Neural stem cells senescence can lead to the decline of nerve repair and regeneration, causing brain aging and neurodegenerative diseases. However, the mechanism underlying neural stem cells senescence remains poorly understood. In this study, we report a novel HO-1/PARP1 non-canonical pathway highlighting how oxidative stress triggers the DNA damage response, ultimately leading to premature cellular senescence in neural stem cells. HO-1 acts as a sensor for oxidative stress, while PARP1 functions as a sensor for DNA damage. The simultaneous expression and molecular interaction of these two sensors can initiate a crosstalk of oxidative stress and DNA damage response processes, leading to the vicious cycle. The persistent activation of this pathway contributes to the senescence of neural stem cells, which in turn plays a crucial role in the progression of neurodegenerative diseases. Consequently, targeting this novel signaling pathway holds promise for the development of innovative therapeutic strategies and targets aimed at mitigating neural stem cells senescence-related disorders.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)