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Astrocytic Metabolic Reprogramming as a Therapeutic Target for Alzheimer’s Disease

Project description

Targeting astrocytic hypermetabolism for Alzheimer’s treatment

Alzheimer’s disease research has traditionally focused on protein plaques, often overlooking the role of astrocytic metabolism. The ERC-funded HyperAstroMet project addresses this by investigating astrocytic hypermetabolism, a state in which brain support cells undergo metabolic reprogramming, characterised by excessive glycolysis and disrupted insulin signalling. This project aims to unravel the link between metabolic dysfunction and neuronal loss to identify new therapeutic targets. Using advanced real-time monitoring, it will explore whether targeting sugar gates like GLUT1 can preserve neuronal integrity. Ultimately, the project’s goal is to provide transformative avenues for treating Alzheimer’s by moving beyond the amyloid-centric paradigm.

Objective

Alzheimer's disease (AD) represents a growing public health challenge, with its prevalence steadily increasing profoundly affecting both patients and their families. Despite extensive research focusing on amyloid-beta and tau as central pathological hallmarks of AD, the crucial role of astrocytic metabolism in neurodegeneration has often been overlooked. The HyperAstroMet project introduces a novel approach by investigating astrocytic hypermetabolism as a pivotal driver of neuronal hyperexcitability, dysfunction, and cognitive decline in AD. Astrocytes, integral to brain energy homeostasis, undergo significant metabolic reprogramming in the context of AD, marked by excessive glycolysis, altered glycogen storage, and disrupted insulin receptor signaling. These metabolic disturbances are thought to contribute to disease progression, yet their precise mechanisms remain poorly understood.
This project aims to unravel the complex interplay between astrocytic metabolic dysfunction and neuronal degeneration in AD. Specifically, it seeks to identify new molecular targets for therapeutic intervention by elucidating how astrocytic hypermetabolism exacerbates neuronal dysfunction. Preliminary data from our lab suggest that targeting astrocytic glycolysis, particularly through GLUT1 ablation, can alleviate cognitive deficits and preserve neuronal integrity, potentially through compensatory upregulation of insulin receptor signaling. However, the underlying mechanisms driving these improvements are still not fully elucidated.
To address these knowledge gaps, HyperAstroMet employs cutting-edge methodologies, to monitor real-time astrocyte and neuronal activity and to dissect the therapeutic potential of targeting astrocytic metabolism. By focusing on astrocytic metabolic dysfunction, this research seeks to provide a transformative shift in the understanding of AD pathogenesis, moving beyond the amyloid-centric paradigm and opening new avenues for treatment and prevention.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-COG

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Host institution

UNIVERSIDAD DE NAVARRA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 999 637,00
Address
CAMPUS UNIVERSITARIO EDIFICIO CENTRAL
31080 PAMPLONA
Spain

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Region
Noreste Comunidad Foral de Navarra Navarra
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 999 637,50

Beneficiaries (1)

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