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Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson's Disease

  • Author(s): Chinta, SJ
  • Woods, G
  • Demaria, M
  • Rane, A
  • Zou, Y
  • McQuade, A
  • Rajagopalan, S
  • Limbad, C
  • Madden, DT
  • Campisi, J
  • Andersen, JK
  • et al.

Published Web Location

http://doi.org/10.1016/j.celrep.2017.12.092
No data is associated with this publication.
Abstract

© 2018 The Authors Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinson's disease (PD). Therapies based on PQ's presumed mechanisms of action have not, however, yielded effective disease therapies. Cellular senescence is an anticancer mechanism that arrests proliferation of replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable of damaging neighboring tissues. Here, we demonstrate that senescent cell markers are preferentially present within astrocytes in PD brain tissues. Additionally, PQ was found to induce astrocytic senescence and an SASP in vitro and in vivo, and senescent cell depletion in the latter protects against PQ-induced neuropathology. Our data suggest that exposure to certain environmental toxins promotes accumulation of senescent cells in the aging brain, which can contribute to dopaminergic neurodegeneration. Therapies that target senescent cells may constitute a strategy for treatment of sporadic PD, for which environmental exposure is a major risk factor. Chinta et al. argue that eliminating senescent cells could hold therapeutic promise for halting progression of sporadic PD, where environmental exposure is a major risk factor. They find that senescence cell depletion abrogates development of neurodegenerative phenotypes associated with systemic PQ exposure, indicating that senescent cells can contribute to neurodegeneration.

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