Name: Andreia Castro

Office: I2.12

School Phone: +351 253 604 835

Email: accastro@med.uminho.pt

Keywords: Protein homeostasis ▪ Protein aggregation ▪ Aging ▪ C. elegans ▪ drug discovery. ▪

About

My main research interest is to study the imbalance of protein homeostasis (proteostasis) associated with neurodegenerative diseases and to understand how proteostasis adaptation and/or enhancement may be beneficial to age-related disorders and constitute important therapeutic approaches. The intriguing pattern of neuron-specific vulnerability that characterizes each disorder may also mirror the differential activities of the components of the proteostasis network (PN) among distinct neuronal sub-types. My overall goal is to contribute to a better understanding of the pathogenesis trigger(s) in neurodegeneration and to the establishment of disease modifying treatments. I established a fast-throughput drug discovery pipeline for neurodegenerative diseases, which utilizes C. elegans and mouse models to determine drug safety and efficacy. Using this approach, I found a mechanistic link between serotonergic signaling and tissue regulation of protein homeostasis with impact on diseases associated with protein aggregation.

Pathogenesis and Therapeutics of Machado-Joseph disease  

Teixeira-Castro A, Ailion M, Jalles A, Brignull HR, Vilaça JL, Dias N, Rodrigues P, Oliveira JF, Neves-Carvalho A, Morimoto RI, Maciel P. Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways. Hum Mol Genet. 2011 Aug 1;20(15):2996-3009. doi: 10.1093/hmg/ddr203. Epub 2011 May 5.

Ferro A1, Carvalho AL, Teixeira-Castro A, Almeida C, Tomé RJ, Cortes L, Rodrigues AJ, Logarinho E, Sequeiros J, Macedo-Ribeiro S, Maciel P. NEDD8: a new ataxin-3 interactor. Biochim Biophys Acta. 2007 Nov;1773(11):1619-27. Epub 2007 Aug 24.

Rodrigues AJ, Neves-Carvalho A, Teixeira-Castro A, Rokka A, Corthals G, Logarinho E, Maciel P. Absence of ataxin-3 leads to enhanced stress response in C. elegans. PLoS One. 2011 Apr 19;6(4):e18512. doi: 10.1371/journal.pone.0018512.

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)

Ribeiro-Samy S, Silva NA, Correlo VM, Fraga JS, Pinto L, Teixeira-Castro AC, Leite-Almeida H, Almeida A, Gimble JM, Sousa N, Salgado AJ, Reis RL. Development and Characterization of PHB-HV based 3D Scaffolds for a Tissue Engineering and Cell-Therapy Combinatorial Approach for Spinal Cord Injury Regeneration. Macromolecular Biosience, (2013), in press