Document Type
Article
Publication Date
2018
Publication Title
Cell Reports
DOI
10.1016/j.celrep.2017.12.092
Abstract
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.
Recommended Citation
Chinta, S. J., Woods, G., Demaria, M., Rane, A., Zou, Y., McQuade, A., . . . Andersen, J. K. (2018). Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to Parkinson's disease. Cell Reports, 22(4), 930-940. doi:10.1016/j.celrep.2017.12.092
Publisher's Statement
Originally published in Cell Reports, 22(4), 930-940. Licensed under CC BY-NC-ND 4.0. The original material can be found here.
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Nervous System Diseases Commons
Comments
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