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Research & Scientists | Neurosciences | People | SARASILVA

 

Name: Sara Silva

Office: I2.03

School Phone: +351 253 604 835

Email: sarasilva@med.uminho.pt

 

 

 

Keywords: Polyglutamine disorders Machado-Joseph disease transgenic mouse models proteostasis preclinical trials therapy

About

Sara Duarte-Silva is a post-doctoral researcher at the Life and Health SciencesResearch Institute (ICVS), University of Minho, Braga, Portugal. She holds aB.Sc. in Applied Biology (2006), and an MSc. in Molecular Genetics (2011) fromthe University of Minho, and a PhD in Health Sciences from the Inter-UniversityDoctoral Programme in Ageing and Chronic Disease (2015). Her main researchinterest is the search of new therapeutic strategies for Machado-Joseph disease(MJD). During her graduated studies, Sara contributed to the development andcharacterization of two MJD transgenic mouse models one of which was shown toclosely mimic the human condition, both at phenotypic and pathologic levels.Sara’s main interest in the search for new therapeutic strategies for MJD, forwhich she has been performing preclinical trials using the CMVMJD135 mousemodel. Using pharmacological approaches targeting proteostasis, she identifiedsome compounds that might be helpful for the treatment of MJD and she alsovalidated the CMVMJD135 mouse model as a valuable tool for preclinical trials.These studies allow, concomitantly to the drug testing, the study of possiblepathogenic mechanisms that might be involved in the disease, includingautophagy, mitochondrial abnormalities, molecular chaperones and ER stress. Oneof her recent challenges is to study the role of glia in the pathogenesis ofMJD.

Out of the main research focus, she is also involved in side projects that involve the study of the function of ataxin-3, the protein that when mutated, is causative of MJD. She's also enrolled in studies involving MAPT protein involved in Alzheimer’s disease with other groups of research in the Neurosciences domain.

Projects

Ataxin-3 and ubiquitin signalling in the nervous system  

Pathogenesis and Therapeutics of Machado-Joseph disease  

Selected Publications

Neves-Carvalho A, Logarinho E, Freitas A, Duarte-Silva S, Costa MC, Silva-Fernandes A, Martins M, Cravino Serra S, Lopes A, Paulson HL, Heutink P, Relvas JB, Maciel P. Dominant negative effect of polyglutamine expansion perturbs normal function of ataxin-3 in neuronal cells. Human Mol Gen, 24(1):100-117 (2015).

Lopes S, Lopes A, Pinto V, Guimarães MR, Sardinha VM, Duarte-Silva S, Pinheiro S, Pizarro J, Oliveira JF, Sousa N, Leite-Almeida H, Sotiropoulos I. Absence of Tau triggers age-dependent sciatic nerve morphofunctional deficits and motor impairment. Aging Cell, 15(2):208-216 (2016)

Silva-Fernandes A, Costa Mdo C, Duarte-Silva S, Oliveira P, Botelho CM, Martins L, Mariz JA, Ferreira T, Ribeiro F, Correia-Neves M, Costa C, Maciel P. Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products. Neurobiol Dis. 2010 Oct;40(1):163-76. doi: 10.1016/j.nbd.2010.05.021. Epub 2010 May 25.

Esteves S, Duarte-Silva S, Neves-Carvalho A, Teixeira-Castro A, Oliveira P, Silva-Fernandes A, Maciel P. Limited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease. PLOS One, 10(10):e0141610 (2015)

Sotiropoulos I, Lopes A, Pinto V, Lopes S, Carlos S, Duarte-Silva S, Neves-Carvalho A, Pinto-Ribeiro F, Pinheiro S, Fernandes R, Almeida A, Sousa N, Leite-Almeida H. Selective impact of Tau loss on nociceptive primary afferents and pain sensation. Exp Neurol, 261:486-493 (2014).

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