20 documents found, page 1 of 2
Rivastigmine-Benzimidazole Hybrids as Promising Multitarget Metal-Modulating Co...
Vicente-Zurdo, David; Brunetti, Leonardo; Piemontese, Luca; Guedes, Beatriz; Cardoso, Sandra M.; Chavarria, Daniel; Borges, Fernanda; Madrid, YolandaWith the goal of combating the multi-faceted Alzheimer's disease (AD), a series of Rivastigmine-Benzimidazole (RIV-BIM) hybrids was recently reported by us as multitarget-directed ligands, thanks to their capacity to tackle important hallmarks of AD. In particular, they exhibited antioxidant activity, acted as cholinesterase inhibitors, and inhibited amyloid-β (Aβ) aggregation. Herein, we moved forward in this ...
The Impact of microRNAs on Mitochondrial Function and Immunity: Relevance to Pa...
Guedes, Beatriz F. S.; Cardoso, Sandra M.; Esteves, A. RaquelParkinson's Disease (PD), the second most common neurodegenerative disorder, is characterised by the severe loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and by the presence of Lewy bodies. PD is diagnosed upon the onset of motor symptoms, such as bradykinesia, resting tremor, rigidity, and postural instability. It is currently accepted that motor symptoms are preceded by non-motor f...
Reduction of class I histone deacetylases ameliorates ER-mitochondria cross-tal...
Marinho, Daniela; Ferreira, Ildete L.; Lorenzoni, Ricardo; Cardoso, Sandra M.; Santana, Isabel; Rego, A. CristinaSeveral molecular mechanisms have been described in Alzheimer's disease (AD), including repressed gene transcription and mitochondrial and endoplasmic reticulum (ER) dysfunction. In this study, we evaluate the potential efficacy of transcriptional modifications exerted by inhibition or knockdown of class I histone deacetylases (HDACs) in ameliorating ER-mitochondria cross-talk in AD models. Data show increased ...
LPS-induced mitochondrial dysfunction regulates innate immunity activation and ...
Esteves, A. Raquel; Silva, Diana F. F.; Banha, Diogo; Candeias, Emanuel; Guedes, Beatriz; Cardoso, Sandra M.Sporadic Parkinson's disease (sPD) is a complex multifactorial disorder which etiology remains elusive. Several mechanisms have been described to contribute to PD development namely mitochondrial dysfunction, activation of inflammatory pathways and the deposition of unfolded proteins such as α-synuclein. Our work shows for the first time that lipopolysaccharide (LPS)-induced activation of innate immunity requir...
The neuromicrobiology of Parkinson's disease: A unifying theory
Munoz-Pinto, Mario F.; Empadinhas, Nuno Miguel da Silva; Cardoso, Sandra M.Recent evidence confirms that PD is indeed a multifactorial disease with different aetiologies and prodromal symptomatology that likely depend on the initial trigger. New players with important roles as triggers, facilitators and aggravators of the PD neurodegenerative process have re-emerged in the last few years, the microbes. Having evolved in association with humans for ages, microbes and their products are...
Novel Donepezil-Arylsulfonamide Hybrids as Multitarget-Directed Ligands for Pot...
Queda, Fausto; Calò, Sonia; Gwizdala, Karolina; Magalhães, João D.; Cardoso, Sandra M.; Chaves, Sílvia; Piemontese, Luca; Santos, M. AméliaAlzheimer's disease (AD) is one of the most devastating neurodegenerative disorders, characterized by multiple pathological features. Therefore, multi-target drug discovery has been one of the most active fields searching for new effective anti-AD therapies. Herein, a series of hybrid compounds are reported which were designed and developed by combining an aryl-sulfonamide function with a benzyl-piperidine moie...
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's D...
Poliseno, Viviana; Chaves, Sílvia; Brunetti, Leonardo; Loiodice, Fulvio; Carrieri, Antonio; Laghezza, Antonio; Tortorella, Paolo; Magalhães, João D.Alzheimer's disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1-5), incl...
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, SílviaPursuing 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 CristinaBackground: 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...
Design, Synthesis, and In Vitro Evaluation of Hydroxybenzimidazole-Donepezil An...
Chaves, Sílvia; Resta, Simonetta; Rinaldo, Federica; Costa, Marina; Josselin, Romane; Gwizdala, Karolina; Piemontese, Luca; Capriati, VitoA series of multi-target-directed ligands (MTDLs), obtained by attachment of a hydroxyphenylbenzimidazole (BIM) unit to donepezil (DNP) active mimetic moiety (benzyl-piperidine/-piperazine) was designed, synthesized, and evaluated as potential anti-Alzheimer's disease (AD) drugs in terms of biological activity (inhibition of acetylcholinesterase (AChE) and β-amyloid (Aβ) aggregation), metal chelation, and neuro...