Visit our Expo - Redox and Inflammation signaling 2012

Session XII : Cell death and neurodegenerative diseases Poster XII, 17
GALANTAMINE PREVENTS THE NEUROTOXICITY INDUCED BY BETA-
AMYLOID PEPTIDE
Joana B Melo 1,2, Carla Sousa 1, Pedro Garção1, Paula Agostinho1,3, Catarina R
Oliveira1,3
1Center for Neurosciences and Cell Biology, 2Institute of Medical Biology and 3Institute
of Biochemistry, Faculty of Medicine, University of Coimbra, Portugal
jbmelo@cnc.cj.uc.pt
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the formation of
senile plaques in patients’ brain, composed by amyloid #-peptide (A#). Several reports
indicate that the degree of #-aggregation seems to be particularly important for the
neurotoxicity of this amyloidogenic peptide. Cholinergic abnormalities, such as severe loss of
nicotinic acetylcholine receptors (nAChRs) are also found in AD brains. Several studies on
brains displaying AD lesions have shown changes in the expression and distribution of
acetylcholinesterase (AChE). Although AChE activity is lost in specific regions of the AD
brain, an increase of AChE activity has also been found to co-localize with A# deposits.
Galantamine, a drug currently approved for the symptomatic treatment of AD, is an inhibitor
of AChE and has an additional activity as an allosteric modulator of nAChRs.
The goal of the current study, using cortical cells as a neuronal model, was to evaluate the
effect of several concentrations of galantamine in the neurotoxicity induced by the synthetic
peptide A#1-40 correlating these results with the state of aggregation of this peptide. We
observed that galantamine prevents, in a concentration dependent manner, the increase of
AChE activity and the neuronal injury induced by A#1-40. As expected, amyloid deposition,
evaluated by Congo Red dye, that positively stains #-sheet conformation and Thioflavin S
dye, is increased in the presence of A#1-40 and the treatment of cells with galantamine
decreases this deposition. However, in a cell-free system, galantamine did not revert amyloid
fibril formation. These results suggest that the neuroprotective role of galantamine could also
be correlated with an effect on the aggregation state of amyloid beta-peptide present in the
patients’ brains.
(Supported by Janssen -Cilag and GAI-Faculty Medicine of University of Coimbra)
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