SubsidieMeestersProbing (Orphan) Nuclear Receptors in Neurodegeneration
NeuRoPROBE aims to develop chemical probes and PROTACs for orphan nuclear receptors TLX and Nurr1 using AI to advance therapeutic strategies against neurodegenerative diseases.
Projectdetails
Introduction
Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, or Multiple Sclerosis are severe health burdens and major global challenges for societies and healthcare systems. Therapeutic interventions in these diseases are not satisfying, since there is no treatment strategy that can halt or reverse disease progression.
Research Challenges
Several failed attempts at finding a cure for neurodegeneration have significantly reduced the interest for further research - yet, more than ever, new approaches are needed. Critically missing are pharmacologically validated targets for efficient neurodegenerative disease treatment, and it is exactly here that NeuRoPROBE aims to close this gap.
Target Identification
The orphan nuclear receptors (NR) tailless homologue (TLX) and nuclear receptor related-1 protein (Nurr1) have been identified in knockout studies as prime candidates. However, ligands for their pharmacological control as tools for therapeutic validation are lacking. NeuRoPROBE will enable pharmacological modulation of these transcription factors as a new and groundbreaking strategy to counteract neurodegeneration.
Project Objectives
To meet its overall aim, NeuRoPROBE will:
- Develop chemical probes (CP) and PROTACs for TLX and Nurr1.
- Employ generative artificial intelligence (AI) for molecular design to accelerate CP and PROTAC development.
- Establish phenotypic cellular models in 3D settings to mimic neurodegeneration.
- Use CPs and PROTACs in the phenotypic models for pharmacological control of TLX and Nurr1 to validate their modulation in neurodegeneration.
Expertise and Impact
This challenging and highly multidisciplinary endeavor will profit from my strong interdisciplinary background in the field of NR ligand discovery and pharmacology as well as in AI-based molecular design. NeuRoPROBE will open new avenues towards regenerative treatments in neurodegeneration, close the gaps in pharmacological control of TLX and Nurr1, and substantially contribute to consolidating AI techniques for structural optimization.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.498.813 |
| Totale projectbegroting | € 1.498.813 |
Tijdlijn
| Startdatum | 1-5-2022 |
| Einddatum | 30-4-2027 |
| Subsidiejaar | 2022 |
Partners & Locaties
Projectpartners
- LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHENpenvoerder
Land(en)
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MANUNKIND: Determinants and Dynamics of Collaborative Exploitation
This project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery.
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressure
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This project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function.
The Ethics of Loneliness and Sociability
This project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field.
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