How dietary phenolics delay neurodegenerative diseases

It is believed that a diet rich in phenolics delays neurodegenerative diseases in the ageing population. However, the mechanistic actions of phenolics in brain health remain under examination. The EU-funded LIMBo project aims to analyse the ability of dietary phenolics to prevent and delay neuroinflammation, a central process in neurodegenerative diseases. The project will focus on metabolites derived from dietary phenolics by investigating their effects in both the established and unknown pathways of microglia cells. LIMBo will deliver essential knowledge that improves understanding of the diversity of phenolic metabolites, their specific impact on neuroinflammation and the potential use as pro-drugs. Moreover, it will produce valuable scientific insights for future implementation of healthy brain diets.

Principal Investigator: Cláudia Nunes dos Santos

Start date: 1 April 2019

End date: 30 September 2025

Funded under: European Research Council

Funding Scheme: ERC – Starting Grant

Grant agreement ID: 804229

DOI 10.3030/804229

Project description

Parkinson’s disease (PD) affects 8.5 million individuals worldwide according to WHO estimates. PD remains cureless and treatments are based on administration of dopamine precursors or analogues. Neuroinflammation is a central hallmark of PD, hwever, no molecule is present in the market to tackle neuroinflammation in PD patients. Neuroinflammation contributes to the exacerbation of the disease, as the release of inflammatory signals leads to reduced neuronal fitness driving to neuronal death.
NEUROSHIELD will address this gap in PD treatment, to ensure an increased quality of life of PD patients, while exploiting this therapeutic market opportunity. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in PD has been considered non-effective or raised long-term usage complications due to adverse side-effects. NEUROSHIELD will employ a novel small molecule tackling neuroinflammation through a yet unexplored pathway, different mechanism to the classic NSAID COX-2 inhibitors mechanism. We have identified a novel potent first-in-class small molecule that is a strong attenuator of neuroinflammation.
NEUROSHIELD aims to explore this new safe, brain-permeable molecule, addressing neuroinflammation in Parkinson’s disease through a novel pathway.

Principal Investigator: Cláudia Nunes dos Santos

Start date: 1 June 2025

End date: 30 November 2026

Funded under: European Research Council

Funding Scheme: ERC – Proof of Concept

Grant agreement ID: 101188579

DOI 10.3030/101188579

Project description

The deCYPher project will develop a standardized platform to profoundly implement artificial intelligence (AI) and machine learning (ML) techniques to overcome current hurdles in industrial biotechnology and truly unlock the full potential in biotech engineering.

The project will apply this platform to solve a pertinent problem in the microbial production of plant secondary metabolites, namely the bio-based production of terpenoids and flavonoids. Based on the Design-Build-Test-Learn (DBTL) cycle deCYPher brings together AI/ML with synthetic biology generating transparency, reproducibility, and modularity – supporting the European Green Deal and the circular economy.

Main innovations:

The development of an AI/ML platform for biotechnology applications

Use, reinforce, and extend existing ELIXIR resources for (meta)data management

Use of an integrated holistic approach in the development chain of a bioprocess

Case studies: economical and sustainable production of oxygenated plant metabolites

Novel insights & deeper understanding of the societal ramifications of using AI/ML and SynBio for industrial biotechnology.

Principal Investigator involved in the project: Cláudia Nunes dos Santos

Funded by: European Union

Link: https://www.decypher.bio/

Project description

Neurodegenerative diseases (NDDs) are a growing health crisis with complex origins and limited treatment options. Early neuroinflammation and dysfunction of the neurovascular unit (NVU), particularly the blood-brain barrier (BBB), are key contributors to disease progression. Plant-based diets rich in polyphenols show promise due to their anti-inflammatory properties, but most dietary polyphenols have low bioavailability. In contrast, polyphenol metabolites (PMs) are more bioavailable and BBB-permeable, yet their role in brain health remains underexplored.

The NEXUS project aims to investigate the impact of selected PMs on systemic inflammation and immune cell infiltration into the brain. Using human iPSC-derived models of the BBB and in vivo validation, NEXUS will explore whether these PMs can help prevent NDD progression by modulating immune interactions. The project brings an innovative, translational approach to nutritional neuroscience and may help shape new dietary strategies for healthy aging, in line with the UN’s 2030 Sustainable Development Goals.

Principal Investigator: Inês Figueira 

Start date: 20 February 2025

End date: 19 August 2026

Funded under: Fundação para a Ciência e a Tecnologia (FCT)

Grant agreement ID: 2023.12203.PEX

DOI https://doi.org/10.54499/2023.12203.PEX

Project description:

Parkinson’s disease (PD) has undergone the fastest growth in prevalence and disability among neurological disorders, being characterized by a complex pathobiology at cellular and molecular level, allied to neurovascular unit (NVU) intricacy. To date, the gold standard for PD study are still animal models of the disease, urging the need for the development of novel and robust human-based microphysiological systems (MPS) in the field.

MISSION aims to establish two new human MPS brain models of PD combining dopaminergic and inflammatory stimuli, better emulating disease pathobiology and cell-cell interactions. To achieve this, we will implement and characterize a two-compartment NVU MPS model of PD as well as more complex three-compartment NVU MPS model of PD.

Our main objective will be to study the complex crosstalk mechanisms underlying chronic diseases, such as PD, by enhancing the excellence and resources in MPS in our team, by expanding international collaborations, and by boosting scientists training and mobility.

In the end, we foresee that such MPS will better recapitulate in vivo brain microenvironment and PD phenotype. They will allow a deeper understanding of disease complexity and test compounds, as a proof of concept for other more relevant cell sources for the future such as patient-derived iPSC.

Principal Investigator: Inês Figueira

Start date: 1 March 2025

End date:  28 February 2027

Funded under: MPS_NOVA Hub: Advanced Microphysiological Systems and Pluripotent Stem Cell Technologies to Unveil Chronic Disease Mechanisms and Host-Microbe Interactions (Twinning)

Grant agreement ID: 101159729

DOI: 10.3030/101159729

Project description

ReMAP-PD aims to develop an innovative human-based “brain-on-a-chip” microphysiological platform that recapitulates key pathological features of Parkinson’s disease (PD) in vitro. By leveraging a novel human cellular model of a brain-on-chip, the project seeks to overcome the limited translational value of traditional animal models for PD, which often fail to accurately predict clinical outcomes. This approach aligns with the 3Rs principles (Replacement, Reduction, and Refinement of animal use) while providing a more physiologically relevant and cost-effective system for disease modelling and drug testing.

The platform will be validated using well-characterised pharmacological compounds to demonstrate its robustness, reproducibility, and predictive capacity. Ultimately, ReMAP-PD aims to facilitate regulatory acceptance and foster engagement with industry stakeholders, accelerating the development of safer and more effective therapeutic strategies for PD while reducing reliance on animal experimentation.

• Start date: 01/06/2026
• End date: 30/11/2027
• Duration:  18 M
• Funded under: EU – Horizon – ERC
• Grant agreement ID: ERC-2025-PoC-101292750 – ReMAP-PD
• DOI: (link to the project): pending

Group Leader

Cláudia Nunes dos Santos is Principal Investigator and Vice-Director for Research at NIMSB. Her research is focused on understanding the role of polyphenols in providing the health benefits associated with consuming bioactive-rich plant foods and understanding the mechanistic basis of these beneficial changes. She is particularly interested in the ability of polyphenols metabolites to reach the brain and prevent or reverse the main hallmarks of neurodegenerative diseases. She received her PhD at University of Lisbon in Plant Biochemistry and conducted her postdoctoral studies at Institute of Technology and Chemistry Biology, Portugal. She then worked as a Research Group Leader of the Molecular Nutrition and Health Lab at ITQB NOVA, before joining NOVA Medical School in Lisbon. She was awarded in 2018 with an ERC starting grant for zooming the link between diet and brain health focused in how phenolic metabolites modulate brain inflammation. Recently she was awarded with an ERC Proof-of-concept focused on a novel small molecule “NeuroShield” for tackling Parkinson’s Disease. She was also involved in a series of EU projects as a group leader and work-package leader (FP7-EUBerry; FP7-BacHBerry; Horizon2020-CHIC) and have attracted funding from Portuguese National Agency. She has published over 100 papers in peer-reviewed journals (H-Index of 35, Web of Science).

ORCID

PhD, Senior Researcher

Inês Figueira is a postdoctoral researcher working at Universidade Nova de Lisboa. Inês holds a PhD in Biochemistry with a specialization in Neurosciences, from ITQB-UNL in 2017. With an MSc in Molecular Biology and Genetics (2011) and a BSc in Biochemistry (2009) from FCUL, Inês focuses her research on understanding the cellular & molecular mechanisms that trigger brain diseases, aiming to prevent their progression and focusing on blood-brain barrier (BBB) dysfunction as a central hallmark. Inês seeks to develop improved cell models of the neurovascular unit (e.g., complex co-culture systems and organ-on-chip) to disclose the potential of small molecules towards neurodegeneration, systemic and (neuro)inflammation, BBB impairment, and Parkinson’s disease. Inês published over 31 international peer-reviewed papers, 7 as the first author (h-index 16). So far, she has 8 awards, one FCT CEEC (BOOST_PD – 2022.00151.CEECIND) and two Exploratory FCT Projects (PERCEPT – 2022.02127.PTDC; NEXUS – 2023.12203.PEX).

ORCID

PhD, Junior Researcher 

Diogo Carregosa‘s main research interest focus on the study of microglia cells and neuroinflammation,  the mechanisms of neuroinflammation and novel approaches to modulate microglia, especially in the context of neurodegenerative diseases, like Parkinson’s Disease.  Diogo Carregosa concluded his PhD in Biomedicine at NOVA Medical School, following a MSc in Biochemistry for Health in 2018 and a BSc in Biochemistry in 2016.

Diogo has been working with microglia cells since 2017. Diogo has experience in the synthesis and characterization of small phenolics, natural and synthetic, and its characterization; in vitro culture of immortalized and primary microglia cells; mice models of neuroinflammation and Parkinson’s Disease; animal behavior analysis; quantification of inflammatory markers in plasma and tissue; as well as, genomic, proteomic, and metabolomic techniques.

Diogo Carregosa has 10 publications in scientific journals, 3 book chapters, and has participated in several international conferences. He has also participated in two COST Actions related to neurodegenerative diseases and Parkinson’s disease. From his work, Diogo has a patent application for the use of small phenolics to treat Neurodegenerative Diseases.

ORCID

PhD, Junior Researcher

Jorge Silva holds a PhD in Pharmaceutical Sciences from the Faculty of Pharmacy of the University of Coimbra, where he investigated the cardioprotective effects of a natural compound in pulmonary arterial hypertension. His research interests focus on the therapeutic potential of natural compounds, spanning fungal infections and, more recently, cardiovascular diseases, senescence, and ageing. His work has been published in highly regarded journals, including Phytomedicine and Pharmacological Research.

Jorge is also actively engaged in science outreach, with a strong interest in communicating scientific knowledge to lay audiences.

ORCID

PhD Fellow

Daniela Marques is a PhD researcher at Universidade Nova de Lisboa, focusing on how physiological relevant microbiota-derived dietary (poly)phenol metabolites influence brain health by the modulation of neuroinflammation status of the brain, in the blood-brain barrier. She is also interested to identify candidate compounds that may be a new strategy to delay and/or postpone the development of neurodegenerative diseases. With a Master’s degree in Experimental Pathology and a Bachelor’s degree in Human Biology, she has established herself in the fields of neuroscience and nutrition. Daniela has co-authored nine published articles and contributed to numerous scientific events through poster and oral communications. She actively participates in research projects such as LIMBo and NEXUS. Beyond research, she has served on PhD committees, organized academic events, and volunteered on task forces. Daniela’s work extends to mentoring undergraduate research projects and disseminating scientific knowledge through webinars and open classes, showcasing her comprehensive engagement in the academic and scientific community.

ORCID

PhD Fellow

Catarina Pinto completed her Integrated Master’s degree in Biological Engineering at Instituto Superior Técnico in 2012. She began her research career at the Gulbenkian Institute of Science (IGC), where she worked in Isabel Gordo’s Evolutionary Biology Lab on antibiotic resistance and bacterial growth dynamics, gaining expertise in microbiology, genetic engineering, molecular biology, functional genomics, and in vivo experimentation.

In 2016, she joined Karina Xavier’s Bacterial Signalling Lab at IGC, focusing on gut microbiota and metabolic profiling. In 2017, she moved to the Faculty of Sciences of the University of Lisbon (FCUL) as laboratory manager in Sara Magalhães’ lab, contributing to research activities and the development of standardized protocols for spider mite colony management.

Since 2019, Catarina has been a member of the Cláudia Nunes dos Santos Lab, initially as laboratory manager and, from 2021 onwards, as a full-time researcher. In 2023, she started her PhD in Health Sciences at NMS-NOVA, where her research focuses on the impact of (poly)phenol metabolites on the intestinal microbiome and inflammation.

ORCID

PhD Fellow

Inês Pires Silva is a PhD student at NOVA Medical School, specializing in Health Sciences, particularly Biomedicine. With a background in Biology and Biopharmaceutical Sciences, her focus is on developing a neurovascular unit-on-chip, inducing a PD-like phenotype, and testing phenolic metabolites as a preventive strategy. Her research integrates microfluidics and neurobiology to create physiologically relevant models for studying the effects of phenolic metabolites in neurodegeneration, aiming to advance neurodegenerative disease research.

ORCID

PhD Fellow

Carlos Rafael-Pita is a PhD student at NOVA Medical School, researching how a (poly)phenol-enriched diet modulates gut microbiota and neuroinflammation in the MPTP mouse model of Parkinson’s disease. He holds an MSc in Biomedical Research from the Faculty of Medicine of Coimbra, where he studied lysosomal dysfunction in endothelial cells during heart failure. He has worked on multiple research projects, including investigating the anti-inflammatory potential of bioactive compounds in endothelial and animal models. His expertise spans cell biology, immunology, metabolism, and molecular nutrition. Passionate about inflammation-driven pathologies, he explores dietary interventions for neurodegenerative diseases. Beyond research, he is dedicated to science communication, using illustrations and digital media to make complex biomedical concepts accessible. Through visual storytelling, he bridges the gap between science and the public, promoting a clearer understanding of health and disease.

ORCID

PhD Fellow

Diogo Louro is a PhD student in Molecular Biosciences at ITQB NOVA in Lisbon. He completed his BSc in Biochemistry in 2022 at NOVA FCT and his MSc in NOVA Biomedical Research at NOVA Medical School in 2024. His research focuses on understanding the potential of small molecules, including dietary compounds and microbiota-derived metabolites, to modulate neuroinflammation—a key hallmark of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. By exploring the mechanisms through which these molecules influence neuroinflammatory pathways, he aims to contribute to the development of novel therapeutic strategies that could mitigate disease progression and improve patient outcomes.

ORCID

PhD Fellow (shared)

Inês Paiva is a PhD student in Sustainable Chemistry in the laboratory of Dr. Rita Ventura at ITQB NOVA – Instituto de Tecnologia Química e Biológica António Xavier and at NIMBS – NOVA Institute for Medical Systems. She holds a BSc in Biochemistry from NOVA School of Science and Technology (2018) and an MSc in Biochemistry for Health from NOVA Medical School (2021), where she studied the neurotrophic effects of carbon monoxide in
microglia-neuron communication. Her current research focuses on the development of novel neuroprotective strategies targeting neuroinflammation, a central feature of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Specifically, she investigates the biological activity of (poly)phenol metabolites. Her project involves the synthesis of new analogues of the most active compounds for structure–activity relationship (SAR) studies, as well as the development of 13C-labelled (poly)phenols and fluorescent poly(phenol) probes to uncover their intracellular fate and mechanisms of action. These studies aim to guide the rational design of (poly)phenolic compounds with improved neuroprotective properties.

Dr. Ventura’s lab LINK

ORCID

PhD Fellow

Liza Hilman is a Registered Nutritionist and a PhD student at Nova Medical School, Universidade NOVA de Lisboa. She holds an MSc in Clinical Nutrition from Roehampton University in London.

Her PhD research focuses on the development, validation, and application of a food frequency questionnaire with a specific emphasis on polyphenol intake in the Portuguese population.

Previously, she worked as Head of Nutrition at a biotech company in London, where she developed and managed educational content, presented at conferences, supported the R&D department, and led the development of a nutrition consulting division. She was also involved in B2C and B2B initiatives, as well as marketing strategies.

Liza began her nutrition career with the NHS Diabetes Prevention Programme, delivering lectures on nutrition, physical activity, and healthy lifestyle, and conducting nutrition and health assessments.

She is the author of a popular science book on nutrition and the creator and speaker of several online nutrition courses and podcasts.

ORCID

PhD Fellow

Marco Faria Zadra is a dedicated researcher with a strong foundation in life sciences and biomedical research. He earned a Bachelor’s degree in Life Sciences with a specialization in Biomedical Research from HAN University of Applied Sciences in the Netherlands. During his studies, he completed two significant internships at the DZNE in Bonn, Germany, under the guidance of Daniele Bano, with the final internship serving as his thesis project. Currently, he is in the final year of a Master’s program in Biomedical Research at NOVA Medical School in Lisbon, where he is conducting his thesis research in the Molecular Health and Nutrition Lab led by Claudia Nunes dos Santos. With dual Italian and Portuguese nationalities, he also holds a European Baccalaureate from Brussels, reflecting a diverse and international educational background.

ORCID

PhD Fellow

Ana Rita Garcia is a fellowship researcher at the NOVA Institute for Medical Systems Biology (NIMSB), in Lisbon, Portugal, and is currently completing her PhD in Pharmacy, with a specialisation in Cellular and Molecular Biology. She holds an MSc in Molecular Biology and Genetics (2020) and a BSc in Biochemistry (2016) from the Faculty of Sciences of the University of Lisbon.

Her research has focused on Neuro-Oncology and Bio-oncology, with particular interest in the cellular and molecular mechanisms underlying the development of breast cancer brain metastases and blood–brain barrier dysfunction. Ana Rita has extensive experience with advanced cellular (2D and 3D) and animal models, as well as a broad range of techniques, including live-cell imaging, confocal microscopy, immunohistochemistry, flow cytometry, qPCR, and organ-on-chip microfabrication.

She has authored 10 international peer-reviewed publications, including three as first author, and has presented her work in 45 scientific communications at national and international conferences.

ORCID

MSc Fellow

Daniela Viana Parente holds a Bachelor’s degree in Biochemistry from NOVA School of Science and Technology. She is currently a Master’s student in Biomedical Research at NOVA Medical School.

MSc Fellow

Alexandre Mendes is currently in the second year of the Master’s degree in Biochemistry for Health at NOVA School of Science and Technology (FCT NOVA). In 2024, he completed a Bachelor’s degree in Biochemistry at the Faculty of Sciences of the University of Porto.

During the final year of his undergraduate studies, he undertook an internship at a research laboratory at ICBAS, where his work focused on the role of microRNAs in the diagnosis and prognosis of psoriasis. Throughout his academic journey, Alexandre has been actively involved in mentoring fellow students and participating in extracurricular initiatives, including the student association of his faculty and the biochemistry student nucleus.