Raghavan, A and Kashyap, R and Sreedevi, P and Jos, S and Chatterjee, S and Alex, A and D'Souza, MN and Giridharan, M and Muddashetty, R and Manjithaya, R and Padavattan, S and Nath, S (2024) Astroglia proliferate upon the biogenesis of tunneling nanotubes via α-synuclein dependent transient nuclear translocation of focal adhesion kinase. In: iScience, 27 (8).
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Abstract
Astroglia play crucial neuroprotective roles by internalizing pathogenic aggregates and facilitating their degradation. Here, we show that α-SYN protofibril-induced organelle toxicities and reactive oxygen species (ROS) cause premature cellular senescence in astrocytes and astrocyte-derived cancer cells, resulting in a transient increase in the biogenesis of tunneling nanotubes (TNTs). TNT-biogenesis and TNT-mediated cell-to-cell transfer lead to clearance of α-SYN-induced organelle toxicities, reduction in cellular ROS levels, and reversal of cellular senescence. Enhanced cell proliferation is seen in the post-recovered cells after recovering from α-SYN-induced organelle toxicities. Further, we show that α-SYN-induced senescence promotes the transient localization of focal adhesion kinase (FAK) in the nucleus. FAK-mediated regulation of Rho-associated kinases plays a significant role in the biogenesis of TNTs and their subsequent proliferation. Our study emphasizes that TNT biogenesis has a potential role in the clearance of α-SYN-induced cellular toxicities, the consequences of which cause enhanced proliferation in the post-recovered astroglia cells. © 2024 The Author(s)
| Item Type: | Journal Article |
|---|---|
| Publication: | iScience |
| Publisher: | Elsevier Inc. |
| Additional Information: | The copyright for this article belongs to the authors. |
| Department/Centre: | Autonomous Societies / Centres > Centre for Brain Research |
| Date Deposited: | 18 Oct 2024 07:04 |
| Last Modified: | 18 Oct 2024 07:04 |
| URI: | http://eprints.iisc.ac.in/id/eprint/86380 |
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