Conserved nicotine-activated neuroprotective pathways involve mitochondrial stress

dc.contributor.authorNourse, J. Brucker, Jr.
dc.contributor.authorHarshefi, Gilad
dc.contributor.authorMarom, Adi
dc.contributor.authorKarmi, Abdelrahaman
dc.contributor.authorBen-Ami, Hagit Cohen
dc.contributor.authorCaldwell, Kim A.
dc.contributor.authorCaldwell, Guy A.
dc.contributor.authorTreinin, Millet
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherUniversity of Alabama Birmingham
dc.contributor.otherHebrew University of Jerusalem
dc.date.accessioned2023-09-29T12:45:06Z
dc.date.available2023-09-29T12:45:06Z
dc.date.issued2021
dc.description.abstractTobacco smoking is a risk factor for several human diseases. Conversely, smoking also reduces the prevalence of Parkinson's disease, whose hallmark is degeneration of substantia nigra dopaminergic neurons (DNs). We use C. elegans as a model to investigate whether tobacco-derived nicotine activates nicotinic acetylcholine receptors (nAChRs) to selectively protect DNs. Using this model, we demonstrate conserved functions of DN-expressed nAChRs. We find that DOP-2, a D3-receptor homolog; MCU-1, a mitochondrial calcium uniporter; PINK-1 (PTEN-induced kinase 1); and PDR-1 (Parkin) are required for nicotine-mediated protection of DNs. Together, our results support involvement of a calcium-modulated, mitochondrial stress-activated PINK1/Parkin-dependent pathway in nicotine-induced neuroprotection. This suggests that nicotine-selective protection of substantia nigra DNs is due to the confluence of two factors: first, their unique vulnerability to mitochondrial stress, which is mitigated by increased mitochondrial quality control due to PINK1 activation, and second, their specific expression of D3-receptors.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationNourse, J. B., Jr., Harshefi, G., Marom, A., Karmi, A., Cohen Ben-Ami, H., Caldwell, K. A., Caldwell, G. A., & Treinin, M. (2021). Conserved nicotine-activated neuroprotective pathways involve mitochondrial stress. In iScience (Vol. 24, Issue 3, p. 102140). Elsevier BV. https://doi.org/10.1016/j.isci.2021.102140
dc.identifier.doi10.1016/j.isci.2021.102140
dc.identifier.orcidhttps://orcid.org/0000-0003-1580-6122
dc.identifier.orcidhttps://orcid.org/0000-0002-2448-2660
dc.identifier.orcidhttps://orcid.org/0000-0002-6949-6353
dc.identifier.orcidhttps://orcid.org/0000-0002-8283-9090
dc.identifier.urihttps://ir.ua.edu/handle/123456789/12375
dc.languageEnglish
dc.language.isoen_US
dc.publisherCell Press
dc.rights.licenseAttribution-NoDerivatives 4.0 International (CC BY-ND 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectMultidisciplinary Sciences
dc.titleConserved nicotine-activated neuroprotective pathways involve mitochondrial stressen_US
dc.typeArticle
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