A chemical biology approach to explore lipid metabolism in neurological disorders

Vliet, D. van der (2025)

Doctoral Thesis

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult. This thesis described a chemical biology approach to explore lipid metabolism in neurological disorders. Novel chemical tools were developed to study lipid metabolizing enzymes and these tools were applied to both mouse and human brain tissues. This revealed potential therapeutic targets involved in lipid metabolism that could be harnessed to treat neuroinflammatory diseases such as Multiple Sclerosis and Alzheimer’s Disease. The integration of chemical biology techniques such as activity-based protein profiling, bio-orthogonal chemistry, targeted lipidomics and proteomics with traditional techniques like gene expression analysis and immunohistochemistry was key to provide a comprehensive understanding of lipid metabolism in these complex neurological diseases. The collaboration of neuroscientists and chemists will be required to develop novel therapies and to gain a fundamental understanding of the human brain.

• Neurodegeneration
• Chemical biology
• Lipid
• Microglia
• Multiple sclerosis
• Alzheimer's Disease
• Endocannabinoid
• Activity-based probes
• MAGL
• Demyelination
• Neuroimmunology

• All authors: Vliet, D. van der
• Supervisor: Stelt, M. van der; Huitinga, I.
• Committee: Ubbink, M.; Kasteren, S.I. van; Bot, I.; Eijk, M. van; Hendriks, J.; Stella, N.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Institute of Chemistry (LIC), Faculty of Science, Leiden University
• Date: 2025-06-24
• Sponsorship: Institute of Chemical Immunology