Published Research

A selection of published, peer-reviewed papers from our team and independent scientists demonstrating the research supporting 1C-01.
Here you can find the papers, the authors, and a brief summary outlining the paper's relevance to our research.

Publication Author(s) Date Summary PDF
Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer's disease models Yu Y., Chen C.Z., Celardo I., Tan B.W.Z., Hurcomb J.D., Leal N.S., Popovic R., Loh S.H.Y., Martins L.M. 2024 View Here, we found that a specific mitochondrial process called one-carbon metabolism is disrupted in Alzheimer's disease. Boosting this pathway genetically or by supplementing with folinic acid improved mitochondrial function in both flies and cells. Human data also showed that genes involved in this pathway affect AD risk, suggesting a new treatment direction. PDF
Mitochondrial one-carbon metabolism and Alzheimer's disease Yu Y., Martins L.M. 2024 View Multiple hallmarks of Alzheimer's disease — including amyloid-β accumulation, tau pathology, and age-related oxidative damage — converge on mitochondrial dysfunction, linked to impaired one-carbon metabolism. Five key cellular processes disrupted in AD (redox balance, NAD⁺ availability, mitochondrial function, genome stability, and DNA methylation) are all connected to the one-carbon pathway. SAM, the brain's primary methyl donor and a product of one-carbon metabolism, is severely depleted in AD brains. Enhancing mitochondrial one-carbon metabolism — through folate, folinic acid, or probiotic-based delivery — represents a viable therapeutic strategy for delaying the onset and progression of Alzheimer's disease. PDF
Blocking dPerk in the intestine suppresses neurodegeneration in a Drosophila model of Parkinson's disease Popovic R., Mukherjee A., Leal N.S., Morris L., Yu Y., Loh S.H.Y., Martins L.M. 2023 View Using PINK1-mutant flies as a Parkinson's model, this study showed that sustained activation of the stress kinase dPerk in intestinal cells causes mitochondrial dysfunction, cell death, and reduced lifespan. Crucially, silencing dPerk specifically in the gut — without touching the brain — was sufficient to rescue dopaminergic neuron loss and restore motor function. The findings add mechanistic weight to the idea that gut dysfunction can drive neurodegeneration, and that interrupting this gut-to-brain stress signal is a viable neuroprotective strategy. PDF
Parp mutations protect from mitochondrial toxicity in Alzheimer's disease Yu Y., Fedele G., Celardo I., Loh S.H.Y., Martins L.M. 2021 View We analysed the metabolomic changes in a fly model of AD and identified a decrease of metabolites associated with nicotinamide metabolism, which is critical for mitochondrial function in neurons. We used combined results in flies and humans to show that increasing the bioavailability of NAD+ is neuroprotective. PDF