Exploring the potencial of cyanobacteria against neurodegenerative diseases with foccus on Alzheimer´s disease

Rodrigues, Flávia de Fátima da Cunha

http://hdl.handle.net/10400.22/29557

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Authors

Rodrigues, Flávia de Fátima da Cunha

Advisor(s)

Martins, Rosário

Grosso, Clara

Ferraz, Ricardo

Abstract(s)

Neurodegenerative diseases (ND), particularly Alzheimer’s disease (AD), affect millions of people arounde the world. Despite their high incidence, there is no cure for theses diseases. The main line of treatment envolves the use of acetylcholisnesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors, such as donepezil, galantamine and rivastigmine. Cyanobacteria have been the target for new therapies against DN. Several in silico, in vitro and in vivo studies have demonstrated the neuroprotective potential of natural products dereived from cyanobacteria, particurlarly in AD. Several strains of cyanobacteria present in CIIMAR’s Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) were evaluated for their cytoxicity in neuroblastoma cells (SH-SY5Y) and fibroblasts (3T3-L1) and for their potential to inhibit the enzymes AChE and BuChE. The followed approach envolves analyzing cyanobacterial fractions from the natural products library (LEGE-NPL) obtained by HPLC and cultivating some strains to produce biomass. For each strain, 8 fractions were obtained, with total of 176 fractions analyzed. Three pure compounds isolated from cyanobacteria were also tested (compounds A4, B2D and C3). The results of the cell viability test, using the MTT assay, showed that the vast majority of the fractions were not toxic. As for the enzyme inhibition tests, based on the Ellman method, the results show no inhibition for most analyzed fractions. In general, the most promising results for were obtained for the LEGE 07175_E, LEGE 11439_A and LEGE 181150_B fractions. Further tests should be carried out using these fractions in order to elucidate their chimical composition. With regard to the analyses of the compounds, in the celular viability assay only compound C3 did not demonstrate cytotoxicity at the studied concentrations. As for the enzymatic assays, none of the compounds inhibit the enzymes in the range of concentrations tested. In summary, further studies should be carried out in order to elucidadte the capability of cyanobacteria as treatment against NDs, as well to clarify the chemical profiles of the most promising fractions.