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 neuron...

Full description

Saved in:

Bibliographic Details
Published in:	Acta neuropathologica communications Vol. 6; no. 1; p. 120
Main Authors:	Nicholatos, Justin W, Francisco, Adam B, Bender, Carolyn A, Yeh, Tiffany, Lugay, Fraz J, Salazar, Jairo E, Glorioso, Christin, Libert, Sergiy
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 08-11-2018 BioMed Central BMC
Subjects:	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology Age Aged Aged, 80 and over Animals Animals, Newborn Apoptosis Apoptosis - drug effects Apoptosis - genetics Brain Brain - drug effects Brain - metabolism Brain - pathology Cancer Cell culture Cell cycle Cell death Cell Death - drug effects Disease Models, Animal Epidemiology Exploratory Behavior - drug effects Female Fibroblasts Gene Expression Regulation - drug effects Gene Expression Regulation - genetics Humans Male Mice Mice, Transgenic Neurodegeneration Neurons Neurons - drug effects Neuroprotection Nicotine Nicotine - metabolism Nicotine - pharmacology Nicotinic Agonists - metabolism Nicotinic Agonists - pharmacology Parkinson Disease - etiology Parkinson Disease - metabolism Parkinson Disease - pathology Parkinson's disease Physiology Signal transduction SIRT6 Sirtuins - genetics Sirtuins - metabolism Smoking Studies Sustainable fashion Neuroprotection SIRT6 Cell death Neurodegeneration Parkinson’s disease Nicotine
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2051-5960 2051-5960
DOI:	10.1186/s40478-018-0625-y