Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717319290 |
| _version_ | 1817995523008757760 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shankar J. Chinta |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T02:07:10Z |
| format | Article |
| id | doaj.art-a50111f1811844c78146b1804f884ac5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-14T02:07:10Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a50111f1811844c78146b1804f884ac52022-12-22T02:18:37ZengElsevierCell Reports2211-12472018-01-0122493094010.1016/j.celrep.2017.12.092Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s DiseaseShankar J. Chinta0Georgia Woods1Marco Demaria2Anand Rane3Ying Zou4Amanda McQuade5Subramanian Rajagopalan6Chandani Limbad7David T. Madden8Judith Campisi9Julie K. Andersen10Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USAExposure 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.http://www.sciencedirect.com/science/article/pii/S2211124717319290agingantagonistic pleiotropyneurodegenerationsenescence-associated secretory phenotypetumor suppression |
| spellingShingle | 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 Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease Cell Reports aging antagonistic pleiotropy neurodegeneration senescence-associated secretory phenotype tumor suppression |
| title | Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease |
| title_full | Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease |
| title_fullStr | Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease |
| title_full_unstemmed | Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease |
| title_short | Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease |
| title_sort | cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to parkinson s disease |
| topic | aging antagonistic pleiotropy neurodegeneration senescence-associated secretory phenotype tumor suppression |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717319290 |
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