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P1–401: The influence of the nervous system on mucociliary activity in the frog palate of Rana pipiens
Author(s) -
Hernandez Carmen J.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.780
Subject(s) - anatomy , biotinylated dextran amine , ganglion , trigeminal ganglion , trigeminal nerve , mucociliary clearance , stimulation , rana , chemistry , medicine , sensory system , biology , neuroscience , lung , axon
Background: Alzheimer s disease (AD) is a multifactorial disorder characterized by progressive loss of memory and cognitive functions. One of the principal hallmarks of AD is the occurence of senile plaques containing a small peptide termed A which contributes to neurodegeneration and subsequent cognitive alterations. Some forms of AD exhibit abnormal -amyloid precursor protein (APP) processing, resulting in increased A production. Objective: In the present work we went on to study A effects on APP metabolism. Methods: A was added exogenously to different types of cells in culture, including primary neuronal cultures. APP processing was monitored by analyzing cell lysates and conditioned medium. Intracellular distribution was also investigated upon addition of the peptide by using APP-GFP fusion constructs. Results: We have shown that the A peptide itself can induce alterations in APP processing. In fact, addition of A to the culture medium not only increases the intracellular levels of holo-APP, but also affects APP by blocking its processing. Consequently, protein-protein interactions with APP and other proteins such as FE65 may be altered. Conclusions: Taken together, the data bring us closer to unravelling the factors that modulate APP intracellular processing and the formation of the different cleavage products, which may contribute to our understanding of the cellular and molecular mechanisms of AD. Acknowledgements: Supported by the EU V (Project DIADEM) and VI Framework Program (Project APOPIS), Fundação para a Ciência e Tecnologia of the Portuguese Ministry of Science and Technology, and Centro de Biologia Celular, of the Universidade de Aveiro.