Sara Duarte-Silva

  • Neurodegeneration
  • Machado-Joseph disease
  • Rett syndrome
  • Preclinical trials
  • Therapy
  • Neuronal circuits
  • Glucocorticoid receptor
  • Bile acids

Sara Duarte Silva is a Junior Researcher at the ICVS, under an FCT Scientific Employment Stimulus contract. She holds a BSc in Applied Biology (2006), a MSc in Molecular Genetics (2011) and a PhD in Health Sciences (2015) from the University of Minho. Due to her interest in translational research, she invested on the development and characterization of transgenic mouse models of Machado-Joseph disease (MJD) and established a complete platform setup for drug testing. She has tested pharmacotherapy approaches, contributing for the discovery of new compounds for possible use in MJD. From the studies resulting of these years, she has obtained evidence for the involvement of glucocorticoid receptors (GR) in the pathogenesis of MJD. Although ground-breaking, these studies highlight that there is still a gap in the understanding of the functional meaning of the dysfunctional GR signaling in this context. Therefore, she is currently trying to decipher the relevance of this cellular mechanism dysfunction to the pathogenesis of MJD, using a multi-disciplinary approach. She has secured a total of 295.000€ in funding (personal salary and two international grants as PI or co-PI). She supervised several students, namely MSc (3 to completion and 2 ongoing) and PhD students (3 ongoing), and several undergraduate students. She is also a member of the Animal Welfare Body of the Life and Health Sciences Research Institute and is part of the teaching staff in several post-graduation courses. She received 4 awards and published a total of 32 original articles (8 as first author) and 2 book chapters summing a h-index of 14.

Scientific Highlights

Campos, A. B.*, Duarte-Silva, S.*, Fernandes, B., das Neves, S. P., Marques, F., Teixeira-Castro, A., Neves-Carvalho, A., Monteiro-Fernandes, D., Portugal, C. C., Socodato, R., Summavielle, T., Ambrósio, A. F., Relvas, J. B., & Maciel, P. (2022). Profiling Microglia in a Mouse Model of Machado-Joseph Disease. Biomedicines, 10(2), 237.

Rosa, A. I.*, Duarte-Silva, S.*, Silva-Fernandes, A., Nunes, M. J., Carvalho, A. N., Rodrigues, E., Gama, M. J., Rodrigues, C. M. P., Maciel, P., & Castro-Caldas, M. (2018). Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson’s Disease. Molecular neurobiology, 55(12), 9139–9155.

Duarte-Silva, S., Neves-Carvalho, A., Soares-Cunha, C., Silva, J. M., Teixeira-Castro, A., Vieira, R., Silva-Fernandes, A., & Maciel, P. (2018). Neuroprotective Effects of Creatine in the CMVMJD135 Mouse Model of Spinocerebellar Ataxia Type 3. Movement disorders : official journal of the Movement Disorder Society, 33(5), 815–826.

Duarte-Silva, S., & Maciel, P. (2018). Pharmacological Therapies for Machado-Joseph Disease. Advances in experimental medicine and biology, 1049, 369–394.

Duarte-Silva, S., Silva-Fernandes, A., Neves-Carvalho, A., Soares-Cunha, C., Teixeira-Castro, A., & Maciel, P. (2016). Combined therapy with m-TOR-dependent and -independent autophagy inducers causes neurotoxicity in a mouse model of Machado-Joseph disease. Neuroscience, 313, 162–173.

Duarte-Silva, S., Neves-Carvalho, A., Soares-Cunha, C., Teixeira-Castro, A., Oliveira, P., Silva-Fernandes, A., & Maciel, P. (2014). Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease. Cerebellum (London, England), 13(6), 713–727.

Silva-Fernandes, A., Duarte-Silva, S., Neves-Carvalho, A., Amorim, M., Soares-Cunha, C., Oliveira, P., Thirstrup, K., Teixeira-Castro, A., & Maciel, P. (2014). Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 11(2), 433–449.

Silva-Fernandes, A., Costa, M.doC., Duarte-Silva, S., Oliveira, P., Botelho, C. M., Martins, L., Mariz, J. A., Ferreira, T., Ribeiro, F., Correia-Neves, M., Costa, C., & Maciel, P. (2010). Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products. Neurobiology of disease, 40(1), 163–176.

Funding and Awards
Pioneer Research award, National Ataxia Foundation, USA, 2022 – Co-Principal Investigator: Dissecting the mechanism of action of TUDCA as a therapeutic for SCA3
Seed Money research award, National Ataxia Foundation, United States (2020-2021) – Principal investigator: Studying the effect of the molecular tweezer CLR01 in a mouse model of SCA3


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