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Molecular Neuroscience and Gene Therapy

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Molecular Neuroscience and Gene Therapy

LAB

About the MNTL

The Molecular Neuroscience and Gene Therapy Laboratory (MNGTL) is interested in the study of the molecular and cellular mechanisms underpinning the pathogenesis of different brain disorders, with a particular focus in Polyglutamine disorders. A better understanding of these mechanisms is key point to the development of new therapeutic strategies based on advanced systems as gene or cell therapies. We combine the use of in vitro systems, with the analysis of biological samples from patients and the development of in vivo models to advance in the understanding of brain diseases pathogenesis and in the development of advanced therapies for these diseases.

 

Team

Clévio Nobrega (Principal Investigator)
David Albuquerque (PhD)
Adriana Marcelo (PhD Student)
Rebekah Koppenol (MSc Student)
Xavier Anastácio (MSc Student)
Adriana Arrulo (MSc Student)
Diogo Teixeira (MSc Student)
 

Selected Publications (2013-2018)

 

Marcelo, A, Brito, F, Carmo-Silva, S, Matos, CA, Alves-Cruzeiro, J, Vasconcelos-Ferreira, A, Koppenol, R, Mendonça, L, Pereira de Almeida, L, NÓBREGA, CLÉVIO (2018). Cordycepin activates autophagy through AMPK phosphorylation to reduce abnormalities in Machado-Joseph disease models. Hum. Mol. Genet. doi: 10.1093/hmg/ddy328.

Matos, CA, Pereira de Almeida, L, NÓBREGA, CLÉVIO (2018). Machado-Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy. J Neurochem. doi: 10.1111/jnc.14541.

Carmo-Silva, S, NÓBREGA, CLÉVIO, Pereira de Almeida, L, Cavadas, C (2017). Unravelling the role of ataxin-2 in metabolism. Trends in Endocrinology and Metabolism. doi:http://dx.doi.org/10.1016/j.tem.2016.12.006

Conceição, M, Mendonça, L, NÓBREGA, CLÉVIO, Gomes, C, Costa, P, Hirai, H, Moreira, JN, Lima, C, Manjunath, N, Pereira de Almeida, L. (2016). Safety profile fo the intravenous administration of brain-targeted stable nucleic acid lipid particles. Data Brief., 6:700-705. doi: 10.1016/j.dib.2016.01.017

Matos, CA, NÓBREGA CLÉVIO, Louros SR, Almeida B, de Almeida, LP, Macedo-Ribeiro S, Carvalho AL. (2016). Ataxin-3 phosphorylation decreases neuronal defects and toxicity in spinocerebellar ataxia type 3 disease models. J Cell Biol, 212:465-480. doi: 10.1083/jcb.201506025

Conceição, M, Mendonça, L, NÓBREGA, CLÉVIO, Gomes, C, Costa, P, Hirai, H, Moreira, JN, Lima, C, Manjunath, N, Pereira de Almeida, L. (2016). Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype. Biomaterials, 82:124-137. doi: 10.1016/j.biomaterials.2015.12.021.

NÓBREGA CLÉVIO, Carmo-Silva S, Albuquerque D, Vasconcelos-Ferreira A, Vijayakumar U-G, Mendonça L, Hirai H, Pereira de Almeida L (2015). Reestablishing Ataxin -2 downregulates translation of mutant ataxin-3 and alleviates Machado-Joseph disease. Brain, 138:3537-54. doi: 10.1093/brain/awv298.

Aveleira C, Botelho M, Carmo-Silva S, Pascoal J, Ferreira-Marques M, NÓBREGA CLÉVIO, Cortes L, Valero J, Sousa-Ferreira L, Álvaro AR, Santana M, Kugler S, Pereira de Almeida L, Cavadas C (2015). Neuropepetide Y stimulates autophagy in hypothalamic neurons. PNAS USA,112:E1642-51. doi: 10.1073/pnas.1416609112.

Mendonça L, NÓBREGA CLÉVIO, Hirai H, Kaspar B, Pereira de Almeida L (2015) Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in a transgenic mouse model of Machado-Joseph disease. Brain, 138:320-35. doi: 10.1093/brain/awu352.

NÓBREGA CLÉVIO*, Nascimento-Ferreira I*, Onofre I, Albuquerque D, Hirai H, Déglon N, Pereira de Almeida L (2014) RNA interference mitigates motor and neuropathological deficits in a cerebellar mouse model of Machado-Joseph disease. PlosOne, 9(8):e100086. *Equal contribution. doi: 10.1371/journal.pone.0100086.

Nascimento-Ferreira I*, NÓBREGA CLÉVIO*, Ferreira-Vasconcelos A, Onofre I, Albuquerque D, Aveleira C, Hirai H, Déglon N, Pereira de Almeida L (2013) Beclin-1 mitigates motor and neuropathological deficits in genetic mouse models of Machado-Joseph disease. Brain, 136:2173-88. *Equal contribution. doi: 10.1093/brain/awt144.

NÓBREGA CLÉVIO*, Nascimento-Ferreira I*, Onofre I, Albuquerque D, Hirai H, Déglon N, Pereira de Almeida L (2013) Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease transgenic mice. PLoS One 8(1):e52396. *Equal contribution. doi: 10.1371/journal.pone.0052396.

NÓBREGA CLÉVIO*, Nascimento-Ferreira I*, Onofre I, Albuquerque D, Conceição M, Déglon N, Pereira de Almeida L (2013) Overexpression of mutant ataxin-3 in mouse cerebellum induces ataxia and cerebellar neuropathology. Cerebellum, 12:441-55 *Equal contribution. doi: 10.1007/s12311-012-0432-0.

 

Projects

 

As Principal Investigator

The role of stress granules in Polyglutamine disease: from pathogenesis to molecular therapy. Funding Agency: Fundação para a Ciência e Tecnologia, October 2018-September 2021.

Neuroprotective therapeutic approach of Spinocerebellar ataxia type 2: pharmacological targeting of AMPK. Funding Agency: ATAXIA UK, United Kingdom, October 2017-December 2019.

Ataxin-2 as a molecular target in Machado-Joseph disease: from translation regulation to disease alleviation. Funding Agency: The French Muscular Dystrophy Association (AFM), France, February 2015-December 2017.

The role of ataxin-2 in Machado-Joseph disease: a molecular therapy approach with viral vectors. Funding Agency: The National Ataxia Foundation (NAF), USA, January 2014-December 2015.

 

Representative Images

 

Team