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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. Raquel

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-alanine (BMAA) ...


Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients

Marques, Ana P.; Resende, Rosa; Silva, Diana F.; Batista, Mariana; Pereira, Daniela; Wildenberg, Brigite; Morais, Sofia; Macedo, António; Pais, Claudia

This study aims to evaluate whether mitochondrial changes occur in the early stages of bipolar disorder (BD). Using fibroblasts derived from BD patients and matched controls, the levels of proteins involved in mitochondrial biogenesis and dynamics (fission and fusion) were evaluated by Western Blot analysis. Mitochondrial membrane potential (MMP) was studied using the fluorescent probe TMRE. Mitochondrial morph...


Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for ...

Fancellu, Gaia; Chand, Karam; Tomás, Daniel; Orlandini, Elisabetta; Piemontese, Luca; Silva, Diana F.; Cardoso, Sandra M.; Chaves, Sílvia

Pursuing the widespread interest on multi-target drugs to combat Alzheimer´s disease (AD), a new series of hybrids was designed and developed based on the repositioning of the well-known acetylcholinesterase (AChE) inhibitor, tacrine (TAC), by its coupling to benzofuran (BF) derivatives. The BF framework aims to endow the conjugate molecules with ability for inhibition of AChE (bimodal way) and of amyloid-beta ...


Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, a...

Silva, Diana F.; Candeias, Emanuel; Esteves, Ana Raquel Fernandes; Magalhães, João Duarte; Ferreira, I. Luísa; Nunes-Costa, Daniela; Rego, Ana Cristina

Background: After decades of research recognizing it as a complex multifactorial disorder, sporadic Alzheimer’s disease (sAD) still has no known etiology. Adding to the myriad of different pathways involved, bacterial neurotoxins are assuming greater importance in the etiology and/or progression of sAD. β-N-Methylamino-L-alanine (BMAA), a neurotoxin produced by some microorganisms namely cyanobacteria, was prev...


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