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Stalling the course of Alzheimer´s disease: can cyanobacteria be a new approach toward therapy?

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Alzheimer's Disease (AD) is a severe, age-related neurodegenerative disease and it is the primary cause of dementia. It is marked by the progressive loss of neurons, accompanied by the presence of amyloid plaques, neurofibrillary tangles, and other pathological changes, including cholinergic deficiency. Currently, there is no cure for AD, and although treatments are available to alleviate symptoms, they do not hinder the advancement of the disease. Acetylcholinesterase inhibitors (AChEIs), such as Donepezil, Galantamine, and Rivastigmine are the main course of treatment, but new, more efficacious, and tolerable medications are needed. Blue biotechnology is leading the search for new bioactive compounds. Cyanobacteria, a heterogeneous group of photosynthetic microorganisms, are a prolific source that has shown promise in the field of AD. The Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) housed at CIIMAR, composed mainly of cyanobacteria strains, is a valuable resource that has been exploited for various biomedical applications. In this work, 22 cyanobacteria strains from the LEGE-CC were evaluated for their cytotoxicity in neuroblastoma cells (SH-SY5Y), endothelial cells representative of the blood-brain barrier (hCMEC/D3), and fibroblasts (3T3-L1), and for their potential to inhibit AChE. The approach included the screening of existing cyanobacterial fractions in the natural products library (LEGE-NPL), cultivating new strains to obtain biomass, preparing methanolic extracts, and HPLC fractionation. For each strain, 8 fractions (A-H) were obtained, with a total of 176 fractions tested. The cell viability results, based on the MTT assay, showed that most of the fractions are not cytotoxic at a concentration of 50 µg/mL, as only 15 showed toxicity, with inhibition of cell viability above 30%. In the in vitro AChE inhibition assay, based on Ellman's method, the fractions Spirulina sp. LEGE 11439_A and Scytonema sp. LEGE 07189_A (500 µg/mL) showed low to moderate inhibition of 29.15% and 21.73%, respectively, which indicates some potential in a preliminary screening. Further research can be undertaken to investigate additional anti-AD activities and to elucidate the chemical profiles of the fractions.

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Alzheimer´s disease Cyanobacteria Citotoxicity Acetylcholinestarase Blue biotechnology

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