Maria Ioannou: Lipid Dynamics, Brain Cell Stress, ApoE, and Neurodegenerative Disorders

About this episode

Lipids (phospholipids, cholesterol, sphingolipids, ceramides, triglycerides, fatty acids, and others) play vital roles as the major building blocks of cell membranes and in energy metabolism, and cell signaling. University of Alberta cell biologist Maria Ioannou is using cutting-edge cell imaging and biochemistry technologies to elucidate how lipids are moved within and between cells, and how those processes are involved in normal brain functions and if and how those processes are altered in neurodegenerative disorders such as Alzheimer's and Parkinson's disease. She discovered that when neurons are subjected to oxidative stress they accumulate oxidized potentially toxic lipids which are then extruded from the neurons in vesicles which are subsequently internalized by adjacent astrocytes thereby preventing damage to the neurons. Apolipoprotein E (ApoE) genotype is a major risk factor for Alzheimer's disease with ApoE4 increasing risk and ApoE2 and ApoE3 decreasing risk. Maria's laboratory provided evidence that the protective ApoEs enhance removal of toxic lipids from neurons wherease ApoE4 exacerbates accumulation of the toxic lipids in neurons Recently her lab provided that excessive accumulation of the lipid glucosylceramide in neurons results in the release of pathological alpha-synuclein in ectosomes which then transfer the alpha-synuclein to adjacent neurons. These finding may help explain how the neurodegenerative process spreads through neural networks in Parkinson's disease.

LINKS

Ioannou laboratory webpage:

https://ioannoulab.com/

Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity

https://www.cell.com/action/showPdf?pii=S0092-8674%2819%2930387-3

Protective ApoE variants support neuronal function by effluxing oxidized phospholipids:

https://www.cell.com/action/showPdf?pii=S0896-6273%2825%2900847-5

Glucosylceramide-induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease:

file:///Users/markmattson/Downloads/s41556-026-01871-6%20(1).pdf