Cell and Molecular Neuroscience Unit
Our research interests are focused on the understanding of the molecular mechanisms which lead to neurodegeneration in diseases such as Parkinson's, Huntington's, or Alzheimer's disease. These diseases are intimately associated with protein misfolding and aggregation in specific regions of the brain.
Because the molecular pathways involved in protein homeostasis are highly conserved, we employ a wide variety of model organisms, from the simple but powerful budding yeast to mammalian cell culture and mice, to study the origin of the problems.
Our ultimate goals are to develop novel therapeutic approaches for these and other related disorders. We are working closely together with clinicians in order to accelerate drug discovery efforts, translating basic research into clinical applications that will improve the lives of patients.
» Research Areas
» Group Leader
» Research Team
Tiago Fleming Outeiro
PhD (2004) at the Whitehead Institute for Biomedical Research, MIT, EUA
Post-doctoral research at Harvard Medical School and at FoldRx Pharmaceuticals, USA
Co-founder of BioEPI Clinical and Translational Research Center, Portugal
» Ongoing Research Projects
2007/2009 - SirT2 as a Drug Target in Parkinson's Disease. Michael J. Fox Foundation.
2007/2009 - Unraveling the genetic basis for alpha-synuclein oligomerization in living cells using bimolecular fluorescence complementation. Michael J. Fox Foundation.
2007/2009 - Deciphering the Molecular Role of DJ-1 in Parkinson's disease, Fundação Calouste Gulbenkian. Fundação Calouste Gulbenkian.
2007/2011 - NEUROFOLD, Uncovering the Molecular Basis of Neurodegenerative Disorders. Marie Curie Program, European Commission. FP7-Comissão Europeia.
2007/2009 - The molecular effects of the novel ACE mutation Q1069R. American Portuguese Biomedical Research Fund.
2008/2009 - Molecular characterization of the Portuguese population affected by neurodegeneratives disorders. Alto Comissariado para a Saúde.
2009/2011 - Doença de Parkinson de Progressão Lenta e Rápida: Determinantes Moleculares e Biomarcadores. Fundação para a Ciência e a Tecnologia, (PIC/IC/82760/2007).
2009/2011 - Axa Research Fund: Doctoral sponsorship agreement. AXA.
2009/2011 - EMBO Installation Grant. European Molecular Biology Organization.
» Science and Society Activities
Flaviano Giorgini (University of Leicester, UK)
Aleksey Kazantsev (Massachusetts General Hospital, Harvard Medical School, USA)
Fran Borovecki (University of Zagreb, Croatia)
Bertrand Joseph (Karolinska Institute, Sweden)
Jia-Yi Li (Lund University, Sweden)
Hilal Lashuel, EPFL (Switzerland)
Jean-Christophe Rochet (Purdue University, USA)
Bradley T. Hyman (Massachusetts General Hospital, Harvard Medical School, USA)
Poul Henning Jensen (University of Arhus, Denmark)
Sub-director of Ciência Hoje (www.cienciahoje.pt).
Organizer of the Lisbon Area Neuroscience Meetings.
Blog of the Scientist an initiative by Ciência Viva, GAPP.
Outeiro, T.F., Soares, R., Massada, J., Vinho Tinto e Envelhecimento: Como nos Protegermos de Alzheimer, FNAC Chiado, Lisboa, Portugal. December 2007.
Outeiro, T.F., Soares, R., Massada, J., Vinho Tinto e Envelhecimento: Como nos Protegermos de Alzheimer, FNAC Norte Shopping, Porto, Portugal. May 2007.
» Selected Publications
2008 Aging Research Prize, Portuguese Society for Neuroscience and Pfizer
2007 Best Scientific Article, Portuguese Society for Neuroscience
2006 Research Talent Award from the Portuguese Government
2006 Science Talent Award from the Portuguese Government
2003 Young Investigator Award, Gordon Research Conference on Triplet Repeat Disorders
» Useful Links
Rosa P, Tenreiro S, Chu V, Outeiro TF, Conde JP. High-throughput study of alpha-synuclein expression in yeast using microfluidics for control of local cellular microenvironment. Biomicrofluidics. 2012 Mar;6(1): 14109-141099.
de Oliveira RM, Sarkander J, Kazantsev AG, Outeiro TF. SIRT2 as a Therapeutic Target for Age-Related Disorders. Front Pharmacol. 2012;3:82. Epub 2012 May 3.
Herrera F, Gonçalves S, Outeiro TF. Imaging protein oligomerization in neurodegeneration using bimolecular fluorescence complementation. Methods Enzymol. 2012;506:157-74.
Herrera F, Outeiro TF. α-Synuclein modifies huntingtin aggregation in living cells. FEBS Lett. 2012 Jan 2;586(1):7-12. Epub 2011 Nov 24.
Ribeiro Morais G*, Vicente Miranda H*, Santos IC, Santos I, Outeiro TF, Paulo A. Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes. Bioorg Med Chem. 2011 Dec 15;19(24):7698-710. Epub 2011 Oct 18.
Näsström T, Gonçalves S, Sahlin C, Nordström E, Screpanti Sundquist V, Lannfelt L, Bergström J, Outeiro TF, Ingelsson M. Antibodies against alpha-synuclein reduce oligomerization in living cells. PLoS One. 2011;6(10):e27230. Epub 2011 Oct 31.
Badiola N, de Oliveira RM, Herrera F, Guardia-Laguarta C, Gonçalves SA, Pera M, Suárez-Calvet M, Clarimon J, Outeiro TF, Lleó A. Tau enhances α-synuclein aggregation and toxicity in cellular models of synucleinopathy. PLoS One. 2011;6(10):e26609.
Martins M, Rosa A, Guedes LC, Fonseca BV, Gotovac K, Violante S, Mestre T, Coelho M, Rosa MM, Martin ER, Vance JM, Outeiro TF, Wang L, Borovecki F, Ferreira JJ, Oliveira SA. Convergence of miRNA expression profiling, α-synuclein interacton and GWAS in Parkinson's disease. PLoS One. 2011;6(10):e25443. Epub 2011 Oct 7.
Swinnen E, Büttner S, Outeiro TF, Galas MC, Madeo F, Winderickx J, Franssens V. Aggresome formation and segregation of inclusions influence toxicity of α-synuclein and synphilin-1 in yeast. Biochem Soc Trans. 2011 Oct;39(5):1476-81. Review.
Outeiro TF. Amyloidogenesis: FlAsH illuminates Aβ aggregation. Nat Chem Biol. 2011 Aug 17;7(9):581-2. doi: 10.1038/nchembio.636.
Marques S, Batalha VL, Lopes LV, Outeiro TF. Modulating Alzheimer's disease through caffeine: a putative link to epigenetics. J Alzheimers Dis. 2011;24 Suppl 2:161-71. Review.
Jorge CD, Ventura R, Maycock C, Outeiro TF, Santos H, Costa J. Assessment of the efficacy of solutes from extremophiles on protein aggregation in cell models of Huntington's and Parkinson's diseases. Neurochem Res. 2011 Jun;36(6):1005-11.
Herrera F, Tenreiro S, Miller-Fleming L, Outeiro TF. Visualization of cell-to-cell transmission of mutant huntingtin oligomers. PLoS Curr. 2011 Feb 11;3:RRN1210.
Hansen C, Angot E, Bergström AL, Steiner JA, Pieri L, Paul G, Outeiro TF, Melki R, Kallunki P, Fog K, Li JY, Brundin P. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest. 2011 Feb;121(2):715-25. doi: 10.1172/JCI43366. Epub 2011 Jan 18.
Büttner S, Delay C, Franssens V, Bammens T, Ruli D, Zaunschirm S, de Oliveira RM, Outeiro TF, Madeo F, Buée L, Galas MC, Winderickx J. Synphilin-1 Enhances α-Synuclein Aggregation in Yeast and Contributes to Cellular Stress and Cell Death in a Sir2-Dependent Manner. PLoS One. 2010 Oct 27;5(10):e13700.
Tauber E, Miller-Fleming L, Mason RP, Kwan W, Clapp J, Butler NJ, Outeiro TF, Muchowski PJ, Giorgini F. Functional gene expression profiling in yeast implicates translational dysfunction in mutant huntingtin toxicity. J Biol Chem. 2010 Nov 2.
de Oliveira RM, Pais TF, Outeiro TF. Sirtuins: common targets in aging and in neurodegeneration. Curr Drug Targets. 2010 Oct;11(10):1270-80.
Tenreiro S, Outeiro TF. Simple is good: yeast models of neurodegeneration. FEMS Yeast Res. 2010 Dec;10(8):970-9
Gonçalves SA, Matos JE, Outeiro TF. Zooming into protein oligomerization in neurodegeneration using BiFC. Trends Biochem Sci. 2010 Nov;35(11):643-51.
Vicente Miranda H, Outeiro TF. The sour side of neurodegenerative disorders: the effects of protein glycation. J Pathol. 2010 May;221(1):13-25.
Su LJ, Auluck PK, Outeiro TF, Yeger-Lotem E, Kritzer JA, Tardiff DF, Strathearn KE, Liu F, Cao S, Hamamichi S, Hill KJ, Caldwell KA, Bell GW, Fraenkel E, Cooper AA, Caldwell GA, McCaffery JM, Rochet JC, Lindquist S. Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson's disease models. Dis Model Mech. 2010 Mar-Apr;3(3-4):194-208.
Outeiro TF, Klucken J, Bercury K, Tetzlaff J, Putcha P, Oliveira LM, Quintas A, McLean PJ, Hyman BT. Dopamine-induced conformational changes in alpha-synuclein. PLoS One. 2009 Sep 4;4(9):e6906.
Mollenhauer B, Cullen V, Kahn I, Krastins B, Outeiro TF, Pepivani I, Ng J, Schulz-Schaeffer W, Kretzschmar HA, McLean PJ, Trenkwalder C, Sarracino DA, Vonsattel JP, Locascio JJ, El-Agnaf OM, Schlossmacher MG. Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol. 2008 Oct;213(2):315-25.
Outeiro TF, Putcha P, Tetzlaff JE, Spoelgen R, Koker M, Carvalho F, Hyman BT, McLean PJ. Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS One. 2008 Apr 2;3(4):e1867. Erratum in: PLoS One. 2008;3(5).
Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT, Kazantsev AG. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science. 2007 Jul 27;317(5837):516-9. Epub 2007 Jun 21.
Outeiro TF, Klucken J, Strathearn KE, Liu F, Nguyen P, Rochet JC, Hyman BT, McLean PJ. Small heat shock proteins protect against alpha-synuclein-induced toxicity and aggregation. Biochem Biophys Res Commun. 2006 Dec 22;351(3):631-8.
Bodner RA, Outeiro TF, Altmann S, Maxwell MM, Cho SH, Hyman BT, McLean PJ, Young AB, Housman DE, Kazantsev AG. Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's and Parkinson's diseases. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4246-51. Epub 2006 Mar 6.
Outeiro TF, Lindquist S. Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science. 2003 Dec 5;302(5651):1772-5.
Willingham S, Outeiro TF, DeVit MJ, Lindquist SL, Muchowski PJ. Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein. Science. 2003 Dec 5;302(5651):1769-72.