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Adding to the myriad of different pathways involved, bacterial neurotoxins are assuming greater importance in the etiology and\/or progression of sAD. \u03b2-<jats:italic>N<\/jats:italic>-Methylamino-<jats:sc>l<\/jats:sc>-alanine (BMAA), a neurotoxin produced by some microorganisms namely cyanobacteria, was previously detected in the brains of AD patients. Indeed, the consumption of BMAA-enriched foods has been proposed to induce amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), which implicated this microbial metabolite in neurodegeneration mechanisms.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Freshly isolated mitochondria from C57BL\/6 mice were treated with BMAA and O<jats:sub>2<\/jats:sub> consumption rates were determined. O<jats:sub>2<\/jats:sub> consumption and glycolysis rates were also measured in mouse primary cortical neuronal cultures. Further, mitochondrial membrane potential and ROS production were evaluated by fluorimetry and the integrity of mitochondrial network was examined by immunofluorescence. Finally, the ability of BMAA to activate neuronal innate immunity was quantified by addressing TLRs (Toll-like receptors) expression, p65 NF-\u03baB translocation into the nucleus, increased expression of NLRP3 (Nod-like receptor 3), and pro-IL-1\u03b2. Caspase-1 activity was evaluated using a colorimetric substrate and mature IL-1\u03b2 levels were also determined by ELISA.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Treatment with BMAA reduced O<jats:sub>2<\/jats:sub> consumption rates in both isolated mitochondria and in primary cortical cultures, with additional reduced glycolytic rates, decrease mitochondrial potential and increased ROS production. The mitochondrial network was found to be fragmented, which resulted in cardiolipin exposure that stimulated inflammasome NLRP3, reinforced by decreased mitochondrial turnover, as indicated by increased p62 levels. BMAA treatment also activated neuronal extracellular TLR4 and intracellular TLR3, inducing p65 NF-\u03baB translocation into the nucleus and activating the transcription of NLRP3 and pro-IL-1\u03b2. Increased caspase-1 activity resulted in elevated levels of mature IL-1\u03b2. These alterations in mitochondrial metabolism and inflammation increased Tau phosphorylation and A\u03b2 peptides production, two hallmarks of AD.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Here we propose a unifying mechanism for AD neurodegeneration in which a microbial toxin can induce mitochondrial dysfunction and activate neuronal innate immunity, which ultimately results in Tau and A\u03b2 pathology. Our data show that neurons, alone, can mount inflammatory responses, a role previously attributed exclusively to glial cells.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-020-02004-y","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T09:02:56Z","timestamp":1604566976000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, and Alzheimer\u2019s disease features in cortical neurons"],"prefix":"10.1186","volume":"17","author":[{"given":"Diana F.","family":"Silva","sequence":"first","affiliation":[]},{"given":"Emanuel","family":"Candeias","sequence":"additional","affiliation":[]},{"given":"A. Raquel","family":"Esteves","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o D.","family":"Magalh\u00e3es","sequence":"additional","affiliation":[]},{"given":"I. 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