The Molecular Neuroscience and Gene Therapy Laboratory

miniatura

Location

Faculty of Sciences and Technology

Laboratory 3.31, Building 8

University of Algarve

Phone: +351 289800100 (ext.7525)

cdnobrega@ualg.pt

Team Members

Clévio Nobrega (Principal Investigator)

Adriana Marcelo (PhD Student)

Catarina Nunes (MSc Student)

Marta Santos (MSc student)

Rebekah Koppenol (MSc Student)

Ricardo Nunes (BCs Student)

Raquel Lourenço (BSc Student)

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 for patients and the development of in vivo models based in the expression of lentiviral vectors addressing the understanding and the treatment of these pathologies.

Team Members

Recent Publications (2011-2016)

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

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

As Team Member

Does the transplantation of mutant ataxin-3-depleted patient-derived NSC alleviates Machado-Joseph disease (MJD)?
Funding Agency: The French Muscular Dystrophy Association (AFM), France
July 2016-December 2017.

Exploring miRNA contribution to amyloid-b-metabolism: development of a novel lentiviral platform for multiple miRNA expression in Alzheimer´s disease
Funding Agency: The Portuguese Science Foundation (FCT), Portugal
January 2013 to December 2014

Silencing Machado-Joseph Disease through the systemic route
Funding Agency: The Portuguese Science Foundation (FCT), Portugal
January 2013 to December 2014

Autophagy modulation in Machado-Joseph disease
Funding Agency: The French Muscular Dystrophy Association (AFM), France
January 2011 to December 2014

The role of calpain-mediated proteolysis of ataxin-3 in Machado-Joseph disease: a molecular therapy approach with viral vectors
Funding Agency: The Portuguese Science Foundation (FCT), Portugal
January 2011 to December 2013

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