Spedding et al. (2026)
- Authors: Michael Spedding, Johannes Aerts, Steve Alexander, Aurélie-Gaëlle Bellozzi Woestelandt, Elena Chiricozzi, Alexandre Henriques, Pierre-Marie Lledo, Jean-Philippe Loeffler, Rushika Perera, Frances Platt, Pierre-François Pradat, Frédérique Rene, Anthony Schapira, Laura St Clair, Kevin Talbot, Maxime Taquet, Michal Toborek, Bradley Turner, Michael Zandi, Pierre Gressens
- Institutes: Spedding Research Solutions SARL, Le Vésinet, France, Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands, School of Life Sciences, University of Nottingham, Nottingham, UK, Inserm UMR1141, Université Paris Cité, Paris, France, UCL Queen Square Institute of Neurology, London, UK
- Publisher: Pharmacological Reviews
- Link: DOI
Summary
This landmark review establishes a biochemical ‘bridge’ between SARS-CoV-2 infection and the accelerated risk of neurodegenerative diseases like Parkinson’s and Alzheimer’s. By identifying glycosphingolipids as central players in both viral entry and neuronal damage, the study opens a new frontier for therapeutic intervention in Long COVID. It suggests that treating metabolic lipid imbalances could potentially prevent or reverse the chronic ‘brain fog’ and cognitive decline affecting millions of patients worldwide.
What was researched?
The research investigated how SARS-CoV-2 disrupts glycosphingolipid (GSL) metabolism and the role these complex fats play in Long COVID and the progression of neurodegenerative diseases.
Why was it researched?
With millions suffering from persistent neurological symptoms after COVID-19, researchers sought to understand the molecular mechanisms that link viral infection to chronic neuroinflammation and brain aging.
How was it researched?
This was a comprehensive multidisciplinary review and meta-analysis coordinated by IUPHAR, synthesizing data from lipidomics, virology, and clinical neurology to map the GSL metabolic pathways affected by the virus.
What has been found?
The study found that SARS-CoV-2 uses GSLs as attachment factors and significantly alters their levels, leading to membrane instability and neurotoxic protein aggregation. These metabolic disruptions mimic the early stages of neurodegeneration, potentially acting as a ‘primer’ for future cognitive decline. The researchers also identified that GSL-modulating compounds like Miglustat 💊 may offer a pathway to restore lipid homeostasis.
Discussion
A key strength is the integration of diverse scientific fields to explain the ‘metabolic scar’ left by COVID-19. However, the review notes that long-term clinical data are still needed to confirm if these lipid changes directly cause late-onset dementia.
Conclusion & Future Work
The paper concludes that glycosphingolipids are essential biomarkers for Long COVID severity and promising targets for drug development. Future research should focus on clinical trials using GSL-modifying therapies to protect the aging brain from post-viral damage.