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- Evaluation of the potential of marine cyanobacteria towards Alzheimer’s diseasePublication . Moreira, Ana Rita; Silva, Ana Margarida; Vieira, Mónica; Martins, RosárioAlzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases (NDs) and the major cause of dementia. Despite the constant efforts to achieve cure, no treatment is currently effective and new approaches are urgently needed. Marine biotechnology has been at the frontline for the bioprospection of natural sources to treat ND. Several marine compounds have already provided evidence for anti-AD drugs by acting in mechanisms such as the inhibition of acetylcholinesterase (AChE). Among marine organisms, cyanobacteria have been recognized as a major source of bioactive compounds and the potential towards AD has been highlighted, namely AChE inhibitors. This project is included in a screening program that aims to evaluate the potential of cyanobacteria from the Culture Collection of CIIMAR -LEGE-CC against AD. In this work, 80 fractions of marine cyanobacteria were screened for the potential to inhibit AChE since this is a proven enzyme target to ameliorate the loss of cholinergic signal and to induce cytotoxicity in the neuroblastoma cell line SHY5Y, in the normal fibroblasts cell line 3T3L1, and in the endothelial cells from central nervous system capillaries hCMEC/D3. Results considering the enzymatic assays and cytotoxic assays revealed that the fractions are not toxic or with low toxicity. The strains Phormidium sp; an unidentified filamentous Synechococcales and Nodosilinea nodulosa revealed moderate toxicity towards AChE.
- Tracing the path between mushrooms and Alzheimer’s Disease—a literature reviewPublication . Silva, Ana Margarida; Preto, Marco; Grosso, Clara; Vieira, Mónica; Delerue-Matos, Cristina; Vasconcelos, Vitor; Reis, Mariana; Barros, Lillian; Martins, RosarioAlzheimer’s disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial origin, current targeted treatments have only managed to reduce or control symptoms, and to date, only two drugs are close to being able to halt its progression. For decades, natural compounds produced by living organisms have been at the forefront of research for new therapies. Mushrooms, which are well-known for their nutritional and medicinal properties, have also been studied for their potential use in the treatment of AD. Natural products derived from mushrooms have shown to be beneficial in several AD-related mechanisms, including the inhibition of acetylcholinesterase (AChE) and β-secretase (BACE 1); the prevention of amyloid beta (Aβ) aggregation and neurotoxicity; and the prevention of Tau expression and aggregation, as well as antioxidant and anti-inflammatory potential. Several studies in the literature relate mushrooms to neurodegenerative diseases. However, to the best of our knowledge, there is no publication that summarizes only AD data. In this context, this review aims to link the therapeutic potential of mushrooms to AD by compiling the anti-AD potential of different mushroom extracts or isolated compounds, targeting known AD-related mechanisms.
- Wild mushrooms for Alzheimer’s diseasePublication . Silva, Margarida Lobo; Reis, Filipa S.; Grosso, Clara; Pérez, Diana Valverde; Barros, Lillian; Martins, RosárioAlzheimer’s disease (AD) is among the most incident, debilitating, and widespread forms of dementia. AD causes the decline of cognitive function, making overall day-to-day tasks difficult and even impossible. Despite extensive research, its origin and progression are still unclear, and no efficient treatment is available to prevent disease progression or mitigate symptoms. Due to the low efficiency in the available treatments, natural compounds have arisen as an alternative. These are gaining crescent relevance and have been explored, given their promising results as immunomodulatory, anti-inflammatory, or neuroprotective factors. Mountain natural resources, specifically mushrooms, are among the most studied sources of bioactive molecules. The Montesinho Natural Park, located in northeast Portugal, has incredible mushroom biodiversity, which has been exploited to obtain health-beneficial compounds, namely with anti-inflammatory potential. This work aimed to study different mushroom extracts and isolated compounds for the prevention and progression of AD. So far, our work aimed at bringing insight into the effect of extract administration in neuroblastoma and endothelial cell lines through the MTT viability assay, as well as studying their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), enzymes known to be involved in AD pathogenesis through a modified Ellman’s method: dry extracts were resuspended in tris-HCl 50mM + 10% DMSO to concentrations between 2 and 0.03125 mg/mL for enzymatic inhibition assays. To be considered promising, extracts must not cause cellular death of over 15-20% and cause enzymatic inhibition. So far, our results using nine mushroom extracts show low-to-no cytotoxicity in concentrations between 100 and 6.25 µg/mL in endothelial and neuroblastoma cell lines. High concentrations of Lycoperdon umbrinum extract caused cytotoxicity levels of approximately 35% in endothelial cells after 24h treatment; different extracts caused cell proliferation in both cell lines, the most evident being 128% in the lowest concentrations of Russula delica and Boletus fragrans. The most promising results were obtained for Boletus aereus, which, while not cytotoxic, inhibited both enzymes by 60%. Around 30% AChE inhibition was achieved for the two highest concentrations of Agaricus silvicola and Boletus fragrans making both extracts good candidates for further studies.