A team at Yale published a JCI Insight study on how the brain defends against Alzheimer’s-related damage from high cellular calcium. They focused on Glyoxalase 1 (GLO1), a protein that helps cells remove toxic byproducts. When animals had excessive cellular calcium, GLO1 expression and activity increased, suggesting a compensatory protective process.
The labs led by Amy Arnsten and Lauren Hachmann Sansing examined a calcium channel called ryanodine receptor 2 (RyR2). RyR2 releases calcium from the smooth endoplasmic reticulum inside cells. When RyR2 stays abnormally active with age, it can leak calcium continuously; previous work links such changes to Alzheimer’s disease and Long COVID. The researchers used animals with genetically altered RyR2 that remained "on" to study constant calcium leak.
They measured GLO1 in the prefrontal cortex and hippocampus and found that GLO1 rose and peaked at 12 months in mice, then declined in older animals. Animals that lost elevated GLO1 showed worse memory in a T-maze, supporting the idea that GLO1 can protect cognition while it remains active. The authors suggest exploring therapies that target GLO1 to prevent or slow neurodegeneration.
Difficult words
- glyoxalase 1 — protein that helps cells remove toxic byproducts.GLO1
- ryanodine receptor 2 — a channel that releases calcium from inside cells.RyR2
- expression — the production level of a gene or protein.
- compensatory — acting to balance or correct a problem.
- hippocampus — a brain area important for memory and learning.
- leak — to escape or flow out slowly from somewhere.
- neurodegeneration — loss of nerve cells and brain function over time.
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- Do you think increasing GLO1 could help people with memory problems? Why or why not?
- How might constant calcium leakage affect everyday brain activities like thinking or attention?
- What kinds of therapies can you imagine that would target a protein such as GLO1?
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