title: Nicotine promotes survival of cells expressing amyloid precursor protein and presenilin: implication for Alzheimer's disease.
abstract: Amyloid-β protein (Aβ) accumulation is one of the major hallmarks of Alzheimer's disease (AD) and plays a crucial role in its pathogenesis. Cellular models whereby amyloid precursor protein (APP) is highly expressed are commonly used to test the efficacy of novel neuroprotective compounds. In addition to Aβ, it is known that mutation in the protein presenilin contributes to early onset AD. Recently, a cellular neuroblastoma model where both APP and presenilin are expressed has become available. Since protective effects of nicotine against various neurotoxins have been observed, this study was designed to determine whether nicotine would also protect against cellular damage induced by APP or APP and presenilin. Wild type neuroblastoma (N2a) cell line, and those transfected with amyloid precursor protein (APP), and the combination of APP and presenilin were pretreated with various concentrations of nicotine and the survivability of the cells were determined by MTT assay. Nicotine dose dependently provided protection against cellular loss in all cell lines, with highest protection in the double transfected (44%) followed by single transfected (30%), and wild type (21%). The effects of nicotine in turn were blocked by mecamylamine, a non-selective nicotinic antagonist. These results suggest differential sensitivity of cell lines representing AD pathology to the protective effects of nicotine and provide further support of therapeutic potential of nicotinic agonists in at least a subtype of AD patients.
authors: Department of Pharmacology, College of Medicine, Howard University, Washington, DC, United States.
authors: Dwayne
authors: D
authors: Brown
authors: Carlana
authors: C
authors: Ramlochansingh
authors: Kebreten F
authors: KF
authors: Manaye
authors: Yousef
authors: Y
authors: Tizabi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D053763:Presenilins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D053763:Presenilins; D008464:Mecamylamine; D009538:Nicotine