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High lithium levels in tobacco may account for reduced incidences of both Parkinson's disease and melanoma in smokers through enhanced β-catenin-mediated activity.
Med Hypotheses. 2019 Oct; 131:109302.MH

Abstract

Parkinson's disease (PD) patients have higher rates of melanoma and vice versa, observations suggesting that the two conditions may share common pathogenic pathways. β-Catenin is a transcriptional cofactor that, when concentrated in the nucleus, upregulates the expression of canonical Wnt target genes, such as Nurr1, many of which are important for neuronal survival. β-Catenin-mediated activity is decreased in sporadic PD as well as in leucine-rich repeat kinase 2 (LRRK2) and β-glucosidase (GBA) mutation cellular models of PD, which is the most common genetic cause of and risk for PD, respectively. In addition, β-catenin expression is significantly decreased in more aggressive and metastatic melanoma. Multiple observational studies have shown smokers to have significantly lower rates of PD as well as melanoma implying that tobacco may contain one or more elements that protect against both conditions. In support, smoker's brains have significantly reduced levels of α-synuclein, a pathological intracellular protein found in PD brain and melanoma cells. Tobacco contains very high lithium levels compared to other plants. Lithium has a broad array of neuroprotective actions, including enhancing autophagy and reducing intracellular α-synuclein levels, and is effective in both neurotoxin and transgenic preclinical PD models. One of lithium's neuroprotective actions is enhancement of β-catenin-mediated activity leading to increased Nurr1 expression through its ability to inhibit glycogen synthase kinase-3 β (GSK-3β). Lithium also has anti-proliferative effects on melanoma cells and the clinical use of lithium is associated with a reduced incidence of melanoma as well as reduced melanoma-associated mortality. This is the first known report hypothesizing that inhaled lithium from smoking may account for the associated reduced rates of both PD and melanoma and that this protection may be mediated, in part, through lithium-induced GSK-3β inhibition and consequent enhanced β-catenin-mediated activity. This hypothesis could be directly tested in clinical trials assessing lithium therapy's ability to affect β-catenin-mediated activity and slow disease progression in patients with PD or melanoma.

Authors+Show Affiliations

Comprehensive Movement Disorders Center, University at Buffalo, 3435 Main Street, 97 Farber Hall, Buffalo, NY 14214, United States. Electronic address: tguttuso@buffalo.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31443765

Citation

Guttuso, Thomas. "High Lithium Levels in Tobacco May Account for Reduced Incidences of Both Parkinson's Disease and Melanoma in Smokers Through Enhanced Β-catenin-mediated Activity." Medical Hypotheses, vol. 131, 2019, p. 109302.
Guttuso T. High lithium levels in tobacco may account for reduced incidences of both Parkinson's disease and melanoma in smokers through enhanced β-catenin-mediated activity. Med Hypotheses. 2019;131:109302.
Guttuso, T. (2019). High lithium levels in tobacco may account for reduced incidences of both Parkinson's disease and melanoma in smokers through enhanced β-catenin-mediated activity. Medical Hypotheses, 131, 109302. https://doi.org/10.1016/j.mehy.2019.109302
Guttuso T. High Lithium Levels in Tobacco May Account for Reduced Incidences of Both Parkinson's Disease and Melanoma in Smokers Through Enhanced Β-catenin-mediated Activity. Med Hypotheses. 2019;131:109302. PubMed PMID: 31443765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High lithium levels in tobacco may account for reduced incidences of both Parkinson's disease and melanoma in smokers through enhanced β-catenin-mediated activity. A1 - Guttuso,Thomas,Jr Y1 - 2019/07/04/ PY - 2019/04/27/received PY - 2019/07/03/accepted PY - 2019/8/25/entrez PY - 2019/8/25/pubmed PY - 2020/2/25/medline KW - Epidemiology KW - Lithium KW - Melanoma KW - Parkinson's disease KW - Smoking SP - 109302 EP - 109302 JF - Medical hypotheses JO - Med Hypotheses VL - 131 N2 - Parkinson's disease (PD) patients have higher rates of melanoma and vice versa, observations suggesting that the two conditions may share common pathogenic pathways. β-Catenin is a transcriptional cofactor that, when concentrated in the nucleus, upregulates the expression of canonical Wnt target genes, such as Nurr1, many of which are important for neuronal survival. β-Catenin-mediated activity is decreased in sporadic PD as well as in leucine-rich repeat kinase 2 (LRRK2) and β-glucosidase (GBA) mutation cellular models of PD, which is the most common genetic cause of and risk for PD, respectively. In addition, β-catenin expression is significantly decreased in more aggressive and metastatic melanoma. Multiple observational studies have shown smokers to have significantly lower rates of PD as well as melanoma implying that tobacco may contain one or more elements that protect against both conditions. In support, smoker's brains have significantly reduced levels of α-synuclein, a pathological intracellular protein found in PD brain and melanoma cells. Tobacco contains very high lithium levels compared to other plants. Lithium has a broad array of neuroprotective actions, including enhancing autophagy and reducing intracellular α-synuclein levels, and is effective in both neurotoxin and transgenic preclinical PD models. One of lithium's neuroprotective actions is enhancement of β-catenin-mediated activity leading to increased Nurr1 expression through its ability to inhibit glycogen synthase kinase-3 β (GSK-3β). Lithium also has anti-proliferative effects on melanoma cells and the clinical use of lithium is associated with a reduced incidence of melanoma as well as reduced melanoma-associated mortality. This is the first known report hypothesizing that inhaled lithium from smoking may account for the associated reduced rates of both PD and melanoma and that this protection may be mediated, in part, through lithium-induced GSK-3β inhibition and consequent enhanced β-catenin-mediated activity. This hypothesis could be directly tested in clinical trials assessing lithium therapy's ability to affect β-catenin-mediated activity and slow disease progression in patients with PD or melanoma. SN - 1532-2777 UR - https://www.unboundmedicine.com/medline/citation/31443765/High_lithium_levels_in_tobacco_may_account_for_reduced_incidences_of_both_Parkinson's_disease_and_melanoma_in_smokers_through_enhanced_β_catenin_mediated_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(19)30463-3 DB - PRIME DP - Unbound Medicine ER -