Fig. 6.

Proposed model of Δ133p53 regulation of astrocyte-mediated neuroprotection and neuroinflammation. Senescent astrocytes are increased in neurodegenerative diseases, including Alzheimer’s disease, and have diminished Δ133p53. Similarly, senescent astrocytes are observed in brain tissues from cancer patients receiving radiation treatment, suggesting that senescent astrocytes may contribute to chronic neuroinflammation in each of these pathologies. These findings are also reproduced in vitro where cellular senescence is induced in irradiated or replicatively exhausted astrocytes and is associated with loss of Δ133p53, adoption of the SASP, and diminished neurotrophic factor production, including IGF-1, which can each be rescued by enhanced expression of Δ133p53. ¹Turnquist et al, 2016; ²current study.