Main Interests:

Our research relies in the hypothesis that brain dysmetabolism is an underlying cause of neurodegenerative diseases such as Parkinson’s or Alzheimer’s.
Epidemiological findings suggest that dysmetabolism such as in Diabetes is an important risk factors for neurodegenerative diseases. Importantly, we identified that protein glycation, a major consequence of hyperglycemia, is a molecular link between these disorders. Therefore, we are focused in understanding how sugar stress potentiates neurodegeneration. This will ultimately allow to identify novel therapeutic targets for brain diseases.

 
 

Research Areas:

Our primary questions are:
1. What is the impact of diabetes (hyperglycemia) in brain diseases?
2. What are the effects of dysbiosis in Parkinson’s disease?
3. Are glycation defenses putative therapeutic agents for Parkinson’s disease?
4. What are the major proteome response mechanisms to glycation in models of brain diseases?

 
 

Experimental Systems:

1. in vitro systems – cell and molecular biology techniques
2. mouse models of the diseases - effects of normo/hypercaloric diets in mice
3. Proteomics and genetic approaches

 
 

Discover more about the DysBrainD: Dysmetabolism in Brain Diseases Lab:

- Doença de Parkinson deixa marcas numa proteína no sangue
- Biomarcadores para a doença de Parkinson | Biomarkers for Parkinson's Disease

 
 
 

2018-2019 – Sugar stress in the brain, Sociedade Portuguesa de Diabetologia, Portugal
(PI: Hugo Vicente Miranda)

2018 - 2020 - Sugar stress in the brain, iNOVA4Health, Portugal
(PI: Hugo Vicente Miranda, Co-PIs: Ricardo Gomes, iBET; Tiago Outeiro, CEDOC)

2016 - 2019 - Targeting the glycation defenses as a protective strategy for Parkinson’s disease, Fundação para a Ciência e Tecnologia, Portugal
(PI: Hugo Vicente Miranda)

2013/2014 - Alpha-synuclein as blood biomarker for Parkinson's Disease, Fundação para a Ciência e Tecnologia, Fundação para a Ciência e Tecnologia, Portugal
(PI: Hugo Vicente Miranda)

Selected Publications:

• Sousa L, Guarda M, Meneses MJ, Macedo MP, Vicente Miranda H. Insulin-degrading enzyme: an ally against metabolic and neurodegenerative diseases. J Pathol. 2021 Aug 16. doi: 10.1002/path.5777. Epub ahead of print. PMID: 34396529.

• Hoffmann AC, Minakaki G, Menges S, Salvi R, Savitskiy S, Kazman A, Vicente Miranda H, Mielenz D, Klucken J, Winkler J, Xiang W. (2019) Extracellular aggregated alpha synuclein primarily triggers lysosomal dysfunction in neural cells prevented by trehalose. Sci Rep. 2019 Jan 24;9(1):544. doi: 10.1038/s41598-018-35811-8.

• König A, Vicente Miranda H, Outeiro TF (2018). Alpha-Synuclein Glycation and the Action of Anti-Diabetic Agents in Parkinson's Disease. J Parkinson’s Disease, 8 (1):33-43. Doi: 10.3233/JPD-171285.

• Ferreira DG, Temido-Ferreira M, Vicente Miranda H, Batalha VL, Coelho JE, Szegö ÉM, Marques-Morgado I, Vaz SH, Rhee JS, Schmitz M, Zerr I, Lopes LV, Outeiro TF (2017). α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B. Nature Neuroscience. 20(11):1569-1579. doi: 10.1038/nn.4648.

• Vicente Miranda H*, Cássio R, Correia-Guedes L, Gomes MA, Chegão A, Miranda E, Soares T, Coelho M, Rosa MM, Ferreira JJ, Outeiro TF* (2017). Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease. Scientific Reports, 7 (1):13713. doi: 10.1038/s41598-017-14175-5.
  * Corresponding author

• Vicente Miranda H, Szego ÉM, Oliveira LM, Breda C, Darendelioglu E, de Oliveira RM, Ferreira DG, Gomes MA, Rott R, Oliveira M, Munari F, Enguita F, Simões T, Rodrigues EF, Heinrich M, Martins IC, Zamolo I, Riess O, Cordeiro C, Ponces-Freire A, Lashuel HA, Santos NC, Lopes LV, Xiang W, Jovin TM, Penque D, Engelender S, Zweckstetter M, Klucken J, Giorgini F, Quintas A, Outeiro TF (2017) Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies. Brain, 140 (5): 1399-1419 doi: 10.1093/brain/awx056

• de Oliveira RM*, Vicente Miranda H*, Francelle L, Pinho R, Szegö ÉM, Martinho R, Munari F, Lázaro DF, Moniot S, Guerreiro P, Fonseca-Ornelas L, Marijanovic Z, Antas P, Gerhardt E, Enguita FJ, Fauvet B, Penque D, Pais TF, Tong Q, Becker S, Kügler S, Lashuel HA, Steegborn C, Zweckstetter M, Outeiro TF. (2017) The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease. PLoS Biol. 15(3):e2000374. doi: 10.1371/journal.pbio.2000374.
  * Co-first authors
  

• Ferreira DG, Batalha VL, Vicente Miranda H, Coelho JE, Gomes R, Gonçalves FQ, Real JI, Rino J, Albino-Teixeira A, Cunha RA, Outeiro TF, Lopes LV (2017). Adenosine A2A Receptors Modulate α-Synuclein Aggregation and Toxicity. Cerebral Cortex. 27(1):718-730. doi: 10.1093/cercor/bhv268.

• 
  Ribeiro Morais G, Palma E, Marques F, Gano L, Oliveira MC, Abrunhosa A, Vicente Miranda H, Outeiro TF, Santos I, Paulo A. (2017) Synthesis and Biological Evaluation of Novel 2-Aryl Benzimidazoles as Chemotherapeutic Agents. Journal of Heterocyclic Chemistry. 54(1):255-267. doi: 10.1002/jhet.2575.

• Vicente Miranda H, Gomes MA, Branco-Santos J, Breda C, Lázaro DF, Lopes LV, Herrera F, Giorgini F, Outeiro TF. (2016) Glycation potentiates neurodegeneration in models of Huntington's disease. Scientific Reports, 18;6:36798. doi: 10.1038/srep36798.

• Vicente Miranda H, El-Agnaf OM, Outeiro TF. (2016) Glycation in Parkinson's disease and Alzheimer's disease. Movement Disorders. 31(6):782-90. doi: 10.1002/mds.26566

• Nunes P, Ribeiro Morais G, Palma E, Silva F, Oliveira MC, Ferreira VFC, Mendes F, Gano L, Vicente Miranda H, Outeiro TF, Santos I, Paulo A. (2015) Isostructural Re(I)/99mTc(I) Tricarbonyl Complexes Functionalized with Benzothiazole Derivatives for Cancer Theranostics, Org Biomol Chem. 14;13(18):5182-94. doi: 10.1039/c5ob00124b

• Macedo D, Tavares L, McDougall GJ, Vicente Miranda H, Stewart D, Ferreira RB, Tenreiro S, Outeiro TF, Santos CN. (2015) (Poly)phenols protect from α-synuclein toxicity by reducing oxidative stress and promoting autophagy. Hum Mol Genet. 2015 Mar 15;24(6):1717-32. doi: 10.1093/hmg/ddu585.

• Vicente Miranda H, Xiang W, de Oliveira RM, Simões T, Pimentel J, Klucken J, Penque D, Outeiro TF, (2013) Heat-mediated enrichment of α-synuclein from cells and tissue for assessing post-translational modifications, J Neurochemistry. 126(5), 673-84. doi: 10.1111/jnc.12251

• Diógenes MJ, Dias RB, Rombo DM, Vicente Miranda H, Maiolino F, Guerreiro P, Näsström T, Franquelim HG, Oliveira LM, Castanho MA, Lannfelt L, Bergström J, Ingelsson M, Quintas A, Sebastião AM, Lopes LV, Outeiro TF. (2012) Extracellular alpha-synuclein oligomers modulate synaptic transmission and impair LTP via NMDA-receptor activation. J Neuroscience 2012 Aug 22;32(34):11750-62. doi:10.1523/JNEUROSCI.0234-12.2012

• 
  Kemppainen S, Rantamäki T, Jerónimo-Santos A, Lavasseur G, Autio H, Karpova N, Kärkkäinen E, Stavén S, Vicente Miranda H, Outeiro TF, Diógenes MJ, Laroche S, Davis S, Sebastião AM, Castrén E, Tanila H.
  (2011) Impaired TrkB receptor signaling contributes to memory impairment in APP/PS1 mice. Neurobiology of Aging. 33(6):1122.e23-39. doi: 10.1016/j.neurobiolaging.2011.11.006.

• Ribeiro Morais G*, Vicente Miranda H*, Santos IC, Santos I, Outeiro TF, Paulo A. (2011) Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes. Bioorg Med Chem. 15;19(24):7698-710. doi: 10.1016/j.bmc.2011.09.065.
  *co-first authors

• Vicente Miranda H, Outeiro TF. (2010) The sour side of neurodegenerative disorders: the effects of protein glycation. Journal of Pathology. 2010 May;221(1):13-25. doi: 10.1002/path.2682.

• Vicente Miranda H, Ferreira AE, Quintas A, Cordeiro C, Freire AP. (2008) Measuring intracellular enzyme concentrations: Assessing the effect of oxidative stress on the amount of glyoxalase I. Biochem Mol Biol Educ. 2008 Mar;36(2):135-8. doi: 10.1002/bmb.20166.

• Gomes RA, Vicente Miranda H, Sousa Silva M, Graça G, Coelho AV, do Nascimento Ferreira AE, Cordeiro C, Freire AP. (2008) Protein glycation and methylglyoxal metabolism in yeast: finding peptide needles in protein haystacks. FEMS Yeast Res. 8(1):174-81. DOI: 10.1111/j.1567-1364.2007.00337.x

• Gomes RA, Vicente Miranda H, Silva MS, Graça G, Coelho AV, Ferreira AE, Cordeiro C, Freire AP.
  (2006) Yeast protein glycation in vivo by methylglyoxal. Molecular modification of glycolytic enzymes and heat shock proteins. FEBS J. 273(23):5273-87. doi: 10.1111/j.1742-4658.2006.05520.x

• Vicente Miranda H, Ferreira AE, Cordeiro C, Freire AP. (2006) Kinetic assay for measurement of enzyme concentration in situ. Anal Biochem. 1;354(1):148-50. doi: 10.1016/j.ab.2005.09.002

• Gomes RA, Sousa Silva M, Vicente Miranda H, Ferreira AE, Cordeiro CA, Freire AP. (2005) Protein glycation in Saccharomyces cerevisiae. Argpyrimidine formation and methylglyoxal catabolism.
  FEBS J. 272(17):4521-31. doi: 10.1111/j.1742-4658.2005.04872.x

Collaborations

• Tiago Fleming Outeiro (CEDOC, NMS|FCM, UNL, Portugal & • Gottingen Medical School, Germany)
• Luísa V. Lopes (iMM, Portugal)
• Maria Paula Macedo (Aveiro University, Portugal)
• Maria José Diógenes (iMM, Portugal)
• Patrícia Gomes-Alves & Ricardo Gomes (iBET, Portugal)
• Joaquim Ferreira & Leonor Correia-Guedes (iMM, Portugal)
• Flaviano Giorgini (Leicester University, UK)
• Wei-Xiang (FAU, Germany)

 
 

Team photos

 
 

Motivated students (Undergraduate, Master and PhD) are encouraged to apply. Interested candidates, please send your CV, a letter explaining your interests and the name/contact information for 1-3 references to Hugo Vicente Miranda (hmvmiranda(at)nms.unl.pt).