10 documents found, page 1 of 1
Neuronal control of microglia through the mitochondria
Pereira-Santos, A. R.; Candeias, Emanuel; Magalhães, J. D.; Empadinhas, Nuno; Esteves, A. Raquel; Cardoso, Sandra MoraisThe microbial toxin β-N-methylamino-L-alanine (BMAA), which is derived from cyanobacteria, targets neuronal mitochondria, leading to the activation of neuronal innate immunity and, consequently, neurodegeneration. Although known to modulate brain inflammation, the precise role of aberrant microglial function in the neurodegenerative process remains elusive. To determine if neurons signal microglial cells, we tr...
The Role of Bacteria-Mitochondria Communication in the Activation of Neuronal I...
Magalhães, João Duarte; Esteves, A. Raquel; Candeias, Emanuel; Silva, Diana F. F.; Empadinhas, Nuno; Cardoso, Sandra MoraisMitochondria play a key role in regulating host metabolism, immunity and cellular homeostasis. Remarkably, these organelles are proposed to have evolved from an endosymbiotic association between an alphaproteobacterium and a primitive eukaryotic host cell or an archaeon. This crucial event determined that human cell mitochondria share some features with bacteria, namely cardiolipin, N-formyl peptides, mtDNA and...
Footprints of a microbial toxin from the gut microbiome to mesencephalic mitoch...
Esteves, A. Raquel; Munoz-Pinto, Mário F; Nunes-Costa, Daniela; Candeias, Emanuel; Silva, Diana F. F.; Magalhães, João Duarte; Santos, A. Raquel PereiraObjective Idiopathic Parkinson’s disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin β-N- methylamino- L- al...
Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans
Gonçalves, Sara; Nunes-Costa, Daniela; Cardoso, Sandra Morais; Empadinhas, Nuno; Marugg, John DavidSerotonin is a phylogenetically ancient compound found in animals, plants, and some bacteria. In eukaryotes, serotonin is synthesized from the aromatic amino acid tryptophan via the key enzymes aromatic amino acid hydroxylase (AAAH) and aromatic amino acid decarboxylase (AAAD). Serotonin is also an intermediate in the melatonin biosynthetic pathway and is involved in several vital functions. In humans, serotoni...
Footprints of a microbial toxin from the gut microbiome to mesencephalic mitoch...
Esteves, A. Raquel; Munoz-Pinto, Mário F.; Nunes-Costa, Daniela; Candeias, Emanuel; Silva, Diana F.; Magalhães, João D.; Pereira-Santos, A. RaquelIdiopathic Parkinson's disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin β-N-methylamino-L-alanine (BMAA) ...
Structural and Functional Alterations in Mitochondria-Associated Membranes (MAM...
Fernandes, Tânia; Resende, Rosa Maria Branco de Matos Costa; Silva, Diana F; Marques, Ana P.; Santos, Armanda Emanuela Castro e; Cardoso, Sandra MoraisAlzheimer's disease (AD) is characterized by the accumulation of extracellular plaques composed by amyloid-β (Aβ) and intracellular neurofibrillary tangles of hyperphosphorylated tau. AD-related neurodegenerative mechanisms involve early changes of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) and impairment of cellular events modulated by these subcellular domains. In this study, we chara...
Macroautophagy and Mitophagy in Neurodegenerative Disorders: Focus on Therapeut...
Magalhães, João Duarte; Fão, Lígia; Vilaça, Rita; Cardoso, Sandra Morais; Rego, A. CristinaMacroautophagy, a quality control mechanism, is an evolutionarily conserved pathway of lysosomal degradation of protein aggregates, pathogens, and damaged organelles. As part of its vital homeostatic role, macroautophagy deregulation is associated with various human disorders, including neurodegenerative diseases. There are several lines of evidence that associate protein misfolding and mitochondrial dysfunctio...
Microbial BMAA and the Pathway for Parkinson's Disease Neurodegeneration
Nunes-Costa, Daniela; Magalhães, João Duarte; G-Fernandes, Maria; Cardoso, Sandra Morais; Empadinhas, NunoThe neurotoxin β-N-methylamino-L-alanine (BMAA) is a natural non-proteinogenic diamino acid produced by several species of both prokaryotic (cyanobacteria) and eukaryotic (diatoms and dinoflagellates) microorganisms. BMAA has been shown to biomagnify through the food chain in some ecosystems, accumulating for example in seafood such as shellfish and fish, common dietary sources of BMAA whose ingestion may have ...
Functional mitochondria are required for amyloid beta-mediated neurotoxicity
Cardoso, Sandra Morais; Santos, Sancha; Swerdlow, Russell H.; Oliveira, Catarina R.The role of mitochondria in amyloid bpeptide (Ab)-induced cytotoxicity is unclear. We therefore exposed NT2 cells, a clonal human teratocarcinoma cell line capable of differentiation into terminal neurons, to Ab 25-35 or to Ab 1-42 to evaluate cell viability and altered mitochondrial function. A 24-h incubation of native NT2 cells (r+ cells) with Ab 25-35 or with Ab 1-42 produced a dose-dependent decline in MTT...
Mitochondrial function is differentially affected upon oxidative stress
Cardoso, Sandra Morais; Pereira, Cláudia; Oliveira, Catarina ResendeThe mechanisms that lead to mitochondrial damage under oxidative stress conditions were examined in synaptosomes treated with ascorbate/iron. A loss of membrane integrity, evaluated by electron microscopy and by LDH leakage, was observed in peroxidized synaptosomes and it was prevented by pre-incubation with vitamin E (150 [mu]M) and idebenone (50 [mu]M). ATP levels decreased, in synaptosomes exposed to ascorba...