Browsing by Author "Karmi, Abdelrahaman"
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Item Conserved nicotine-activated neuroprotective pathways involve mitochondrial stress(Cell Press, 2021) Nourse, J. Brucker, Jr.; Harshefi, Gilad; Marom, Adi; Karmi, Abdelrahaman; Ben-Ami, Hagit Cohen; Caldwell, Kim A.; Caldwell, Guy A.; Treinin, Millet; University of Alabama Tuscaloosa; University of Alabama Birmingham; Hebrew University of JerusalemTobacco 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.