Project description:

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: 31 January 2026

Funded under: European Research Council

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 incurable and treatments are based on the administration of dopamine precursors or analogues. Neuroinflammation is a central hallmark of PD; however, 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 leading to neuronal death.
NEUROSHIELD will address this gap in PD treatment to ensure an increased quality of life for PD patients, while exploiting this therapeutic market opportunity. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in PD has been considered ineffective or raises long-term usage complications due to adverse side effects. NEUROSHIELD will employ a novel small molecule tackling neuroinflammation through a yet unexplored pathway, a 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

Grant agreement ID: 101188579

DOI 10.3030/101188579

Project description:

Vision impairment is a major health challenge worldwide, and our project seeks to uncover the molecular and metabolic mechanisms that could unlock the regenerative capacity of the human retina. While zebrafish can naturally regenerate their retinas through Müller glia reprogramming, mammals lack this ability, leaving diseases such as glaucoma, macular degeneration, and diabetic retinopathy without regenerative treatments. Building on our findings that metabolic reprogramming drives tissue repair, we will investigate how protein lactylation and O-GlcNAcylation regulate Müller glia dedifferentiation during zebrafish retina regeneration, and test whether similar mechanisms can be activated in human retinal organoids.

By combining these complementary systems, the project aims to reveal conserved metabolic adaptations across species and pave the way for new therapeutic strategies to restore vision and counteract retinal diseases.

Principal Investigator: António Jacinto

Start date: 1 October 2025

End date: 31 March 2028

Funded under: Fundação para a Ciência e a Tecnologia

Funding scheme: FEDER / Programa Regional de Lisboa 2030

Grant agreement ID: 15085

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—pyrogallol-sulfate, phloroglucinol-sulfate, and resorcinol-sulfate—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 Margarida Lourenço 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