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

Chinta, S. J., Woods, G., Demaria, M., Rane, A., Zou, Y., McQuade, A., Rajagopalan, S., Limbad, C., Madden, D. T., Campisi, J. & Andersen, J. K., 23-Jan-2018, In : Cell reports. 22, 4, p. 930-940 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Shankar J Chinta
  • Georgia Woods
  • Marco Demaria
  • Anand Rane
  • Ying Zou
  • Amanda McQuade
  • Subramanian Rajagopalan
  • Chandani Limbad
  • David T Madden
  • Judith Campisi
  • Julie K Andersen

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.

Original languageEnglish
Pages (from-to)930-940
Number of pages11
JournalCell reports
Volume22
Issue number4
Publication statusPublished - 23-Jan-2018

    Keywords

  • SECRETORY PHENOTYPE, IN-VIVO, CELLS, MICE, STRESS, NEURODEGENERATION, NEUROGENESIS, DEGENERATION, HIPPOCAMPUS, ASTROCYTES

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