Astroglia proliferate upon biogenesis of tunneling nanotubes via α-synuclein dependent transient nuclear translocation of focal adhesion kinase

Abstract

Abstract Astroglia play crucial neuroprotective roles by internalizing pathogenic aggregates and facilitating its degradation. Here, we show, that α-SYN protofibril-induced organelle toxicities and reactive oxygen species (ROS) cause premature cellular senescence in astrocytes and astrocytes origin cancer cells, resulting in a transient increase in 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 relieving from α-SYN-induced organelle toxicities. Further, we show, that α-SYN-induced senescence promotes 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 successively proliferation. Our study emphasizes that TNT biogenesis has a potential role in the clearance of α-SYN-induced cellular toxicities and reversal of stress-induced cellular senescence, consequences of which cause enhanced proliferation in the post-recovered astroglia cells.