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The Protective Effects of Nicotine in Cells Expressing Beta Amyloid and Presenilin: Implications for Alzheimer's Disease
Author(s) -
BROWN DWAYNE,
Ramlochansingh Carlana,
Tizabi Yousef,
Manaye Kebreten F,
Drew Amy C.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.846.2
Subject(s) - nicotine , presenilin , mecamylamine , pharmacology , amyloid beta , nicotinic agonist , alzheimer's disease , medicine , receptor , chemistry , disease
Alzheimer's disease (AD) is a progressive age‐related neurodegenerative disease characterized by cognitive impairments and formation of plaques and tangles. In addition to Aβ, the major component of plaques, mutation in the protein presenilin has also been shown to contribute to AD's pathology. Since protective effects of nicotine against several neuronal toxins have been observed both in‐vivo and in‐vitro, we hypothesized that nicotine would also protect against cellular damage or death due to high expression of Aβ alone or Aβ and presenilin. We also sought to determine whether this effect by nicotine is mediated through nicotinic receptors. A wild type neuroblastoma (N2a) cell line, one transfected with APP 695 (N2a‐695) and another with the combination of APP 695 and presenilin (N2a‐695+P) were pretreated with various concentrations of nicotine 24 hours after plating. The survival of the cells was determined and nicotine treatment dose‐dependently provided protection against cellular loss. 0.01uM nicotine resulted in a 22% increase in protection in N2a cells, 33% in the N2a‐695 and 44% in the N2a‐695+P cells. These results suggest a differential sensitivity to the protective effects of nicotine in cells representative of AD pathology. Nicotine effects were blocked by mecamylamine pre‐treatment. Although the mechanism for the nicotine‐induced protection is not known, the data suggest that nicotinic agonists could be of therapeutic use in AD.