DysBrainD - Dysmetabolism in Brain Diseases laboratory

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 Diabetes mellitus type 2 is an important risk factor for neurodegenerative diseases. The DysBrainD is focused in dissecting the molecular links between these diseases, to unveil novel causes for Neurodegenerative diseases.

We are currently investigating how glycation, reaction between sugars and biomolecules, is affecting the brain at a protein level (proteomics), all way to how it affects animal models (rodents) behaviour (motor and non-motor).

We are also investigating how sugar stress potentiates neurodegeneration and if compensating dysregulated proteins such as the insulin-degrading enzyme have therapeutic potential for Parkinson's disease.

The DysBrainD employs a translational approach from cells and animal models, to patient-derived cells and to the evaluation of Patient cohorts, aiming to identify novel biomarkers and disease-altering therapeutics for neurodegenerative diseases, particularly, for Parkinson's disease.

Graphical Abstract
  • 2021-2022 - Insulin-degrading enzyme as a marker to identify type II diabetes patients at risk of developing Parkinson's disease, Sociedade Portuguesa de Diabetologia, Portugal
    (PI: Hugo Vicente Miranda)
    We aim to explore if changes in the levels/activity of insulin-degrading enzyme in the blood are able to discriminate between Parkinson's disease, type-2 diabetes and healthy individuals
  • 2018 - 2021 - Sugar stress in the brain, iNOVA4Health, Portugal
    (PI: Hugo Vicente Miranda, Co-PIs: Ricardo Gomes, iBET; Tiago Outeiro, CEDOC)
    In this project, we are investigating at a proteome level, the impact of glycation in different brain regions of a mouse model of Parkinson's disease.
  • 2018-2019 – Sugar stress in the brain, Sociedade Portuguesa de Diabetologia, Portugal
    (PI: Hugo Vicente Miranda)
    We focused on the impact of high-fat, high-sucrose diet in the brain, to establish a connection between the development of type II diabetes and Parkinson's disease
  • 2016 - 2020 - Targeting the glycation defenses as a protective strategy for Parkinson’s disease, Fundação para a Ciência e Tecnologia, Portugal
    (PI: Hugo Vicente Miranda)
    This project aimed at establishing glycation as a causative event for Parkinson's disease, and to investigate if the suppression of glycation holds therapeutic potential for Parkinson's disease.
  • 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)
    In this project, we investigated if alpha-synuclein posttranslational modifications (PTMs) in the blood are differentially present in Parkinson's disease patients, and if the measurement of alpha-synuclein PTMs hold diagnostic potential.

Vicente Miranda H*#, Chegão A*, Oliveira MS*, Fernandes Gomes B, Enguita FJ, Outeiro TF#. Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein. 2020. FASEB J. 34 (5): 6718-6728.

Hoffmann AC, Minakaki G, Menges S, Salvi R, Savitskiy S, Kazman A, Vicente Miranda H, Mielenz D, Klucken J, Winkler J, Xiang W. Extracellular aggregated alpha synuclein primarily triggers lysosomal dysfunction in neural cells prevented by trehalose. 2019. Scientific Reports. Jan 24;9(1):544.

König A, Vicente Miranda H, Outeiro TF. Alpha-Synuclein Glycation and the Action of Anti-Diabetic Agents in Parkinson's Disease. 2018. J Parkinsons Dis;8(1):33-43.

Vicente Miranda H#, Cássio R, Correia-Guedes L, Gomes MA, Chegão A, Miranda E, Soares T, Coelho M, Rosa MM, Ferreira JJ, Outeiro TF#. Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease. 2017. Scientific Reports. Oct 20;7(1):13713.

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. α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B. 2017. Nature Neuroscience. Nov;20(11):1569-1579.

Vicente Miranda H, Szego ÉM, Oliveira LMA, Breda C, Darendelioglu E, de Oliveira RM, Ferreira DG, Gomes MA, Rott R, Oliveira M, Munari F, Enguita FJ, 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. Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies. 2017. Brain. May 1;140(5):1399-1419.

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. The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease. 2017. PLOS Biology. Mar 3;15(3):e2000374.

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

Vicente Miranda H, El-Agnaf OM, Outeiro TF. Glycation in Parkinson's disease and Alzheimer's disease. 2016. Movement Disorders. Jun;31(6):782-90.

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. Adenosine A2A Receptors Modulate α-Synuclein Aggregation and Toxicity. 2017. Cerebral Cortex. Jan 1;27(1):718-730.

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

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. Isostructural Re(I)/99mTc(I) Tricarbonyl Complexes Functionalized with Benzothiazole Derivatives for Cancer Theranostics. 2015. 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. (Poly)phenols protect from α-synuclein toxicity by reducing oxidative stress and promoting autophagy. 2015. Human Molecular Genetics. Mar 15;24(6):1717-32.

Vicente Miranda H, Xiang W, de Oliveira RM, Simões T, Pimentel J, Klucken J, Penque D, Outeiro TF. Heat-mediated enrichment of α-synuclein from cells and tissue for assessing post-translational modifications. 2013. Journal of Neurochemistry. Sep;12

  • 2021 - Prize at Sociedade Portuguesa de Diabetologia (GIFT prize)
    Hugo Vicente Miranda
  • 2021 - Poster Award at ENCODS 2021 Virtual Meeting
    Ana Chegão
  • 2014 - Poster Award at 8th EHDN Plenary Meeting (Barcelona)
    Hugo Vicente Miranda
Ana Chegão Ganha 'Melhor Poster' na Conferência Encods

A aluna de doutoramento Ana Chegão participou na European Neuroscience Conference by Doctoral Students (ENCODS), em parceria com a FENS.

Hugo Vicente Miranda recebe Prémio Nacional da Diabetologia

O investigador principal recebeu o Prémio Nacional da Diabetologia atribuído pela Sociedade Portuguesa de Diabetologia (SPD) para desenvolver um projeto que associa a diabetes e a doença de Parkinson.

Link between Parkinson's and diabetes featured in the media

The research from the DysBrainD group, led by Hugo Vicente Miranda, was published in npj Parkinson's Disease journal and has researcher Ana Chegão as the first author.

  • Tiago Fleming Outeiro (Gottingen Medical School, Germany)
  • Luísa V. Lopes (iMM, Portugal)
  • Maria Paula Macedo (CEDOC, NMS & Aveiro University, Portugal)
  • Rune Matthiessen (CEDOC, NMS, 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)

Principal Investigator

Hugo Vicente Miranda
Principal Investigator

Team

Ana Chegão
PhD candidate
José Feliz
PhD Student, MD
Luís Sousa
PhD candidate
Adriana Capucho
Master Student
Rafaela Pina
MSc Student