Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6
Parkinson’s disease is characterized by progressive death of dopaminergic neurons, leading to motor and cognitive dysfunction. Epidemiological studies consistently show that the use of tobacco reduces the risk of Parkinson’s. We report that nicotine reduces the abundance of SIRT6 in neuronal culture...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central
2018
|
| Online Access: | http://hdl.handle.net/1721.1/119020 https://orcid.org/0000-0001-8200-6665 |
| _version_ | 1811090423438901248 |
|---|---|
| author | Nicholatos, Justin W Francisco, Adam B Bender, Carolyn A Yeh, Tiffany Lugay, Fraz J Salazar, Jairo E Libert, Sergiy Nicholatos, Justin W. Francisco, Adam B. Bender, Carolyn A. Lugay, Fraz J. Salazar, Jairo E. Glorioso, Christin A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Nicholatos, Justin W Francisco, Adam B Bender, Carolyn A Yeh, Tiffany Lugay, Fraz J Salazar, Jairo E Libert, Sergiy Nicholatos, Justin W. Francisco, Adam B. Bender, Carolyn A. Lugay, Fraz J. Salazar, Jairo E. Glorioso, Christin A. |
| author_sort | Nicholatos, Justin W |
| collection | MIT |
| description | Parkinson’s disease is characterized by progressive death of dopaminergic neurons, leading to motor and cognitive dysfunction. Epidemiological studies consistently show that the use of tobacco reduces the risk of Parkinson’s. We report that nicotine reduces the abundance of SIRT6 in neuronal culture and brain tissue. We find that reduction of SIRT6 is partly responsible for neuroprotection afforded by nicotine. Additionally, SIRT6 abundance is greater in Parkinson’s patient brains, and decreased in the brains of tobacco users. We also identify SNPs that promote SIRT6 expression and simultaneously associate with an increased risk of Parkinson’s. Furthermore, brain-specific SIRT6 knockout mice are protected from MPTP-induced Parkinson’s, while SIRT6 overexpressing mice develop more severe pathology. Our data suggest that SIRT6 plays a pathogenic and pro-inflammatory role in Parkinson’s and that nicotine can provide neuroprotection by accelerating its degradation. Inhibition of SIRT6 may be a promising strategy to ameliorate Parkinson’s and neurodegeneration. Keywords: Parkinson's disease; SIRT6; Nicotine; Neuroprotection; Neurodegeneration; Cell death |
| first_indexed | 2024-09-23T14:45:25Z |
| format | Article |
| id | mit-1721.1/119020 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:45:25Z |
| publishDate | 2018 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1190202022-10-01T22:18:38Z Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6 Nicholatos, Justin W Francisco, Adam B Bender, Carolyn A Yeh, Tiffany Lugay, Fraz J Salazar, Jairo E Libert, Sergiy Nicholatos, Justin W. Francisco, Adam B. Bender, Carolyn A. Lugay, Fraz J. Salazar, Jairo E. Glorioso, Christin A. Massachusetts Institute of Technology. Department of Biology Glorioso, Christin A. Parkinson’s disease is characterized by progressive death of dopaminergic neurons, leading to motor and cognitive dysfunction. Epidemiological studies consistently show that the use of tobacco reduces the risk of Parkinson’s. We report that nicotine reduces the abundance of SIRT6 in neuronal culture and brain tissue. We find that reduction of SIRT6 is partly responsible for neuroprotection afforded by nicotine. Additionally, SIRT6 abundance is greater in Parkinson’s patient brains, and decreased in the brains of tobacco users. We also identify SNPs that promote SIRT6 expression and simultaneously associate with an increased risk of Parkinson’s. Furthermore, brain-specific SIRT6 knockout mice are protected from MPTP-induced Parkinson’s, while SIRT6 overexpressing mice develop more severe pathology. Our data suggest that SIRT6 plays a pathogenic and pro-inflammatory role in Parkinson’s and that nicotine can provide neuroprotection by accelerating its degradation. Inhibition of SIRT6 may be a promising strategy to ameliorate Parkinson’s and neurodegeneration. Keywords: Parkinson's disease; SIRT6; Nicotine; Neuroprotection; Neurodegeneration; Cell death 2018-11-15T14:19:44Z 2018-11-15T14:19:44Z 2018-11 2018-10 2018-11-11T06:30:41Z Article http://purl.org/eprint/type/JournalArticle 2051-5960 http://hdl.handle.net/1721.1/119020 Nicholatos, Justin W. et al. "Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6." Acta Neuropathologica Communications 2018, 6 (November 2018): 120 © 2018 The Authors https://orcid.org/0000-0001-8200-6665 en https://doi.org/10.1186/s40478-018-0625-y Acta Neuropathologica Communications Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ The Author(s). application/pdf BioMed Central BioMed Central |
| spellingShingle | Nicholatos, Justin W Francisco, Adam B Bender, Carolyn A Yeh, Tiffany Lugay, Fraz J Salazar, Jairo E Libert, Sergiy Nicholatos, Justin W. Francisco, Adam B. Bender, Carolyn A. Lugay, Fraz J. Salazar, Jairo E. Glorioso, Christin A. Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6 |
| title | Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6 |
| title_full | Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6 |
| title_fullStr | Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6 |
| title_full_unstemmed | Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6 |
| title_short | Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6 |
| title_sort | nicotine promotes neuron survival and partially protects from parkinson s disease by suppressing sirt6 |
| url | http://hdl.handle.net/1721.1/119020 https://orcid.org/0000-0001-8200-6665 |
| work_keys_str_mv | AT nicholatosjustinw nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT franciscoadamb nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT bendercarolyna nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT yehtiffany nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT lugayfrazj nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT salazarjairoe nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT libertsergiy nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT nicholatosjustinw nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT franciscoadamb nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT bendercarolyna nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT lugayfrazj nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT salazarjairoe nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 AT gloriosochristina nicotinepromotesneuronsurvivalandpartiallyprotectsfromparkinsonsdiseasebysuppressingsirt6 |