Good news!
"Key points
- High levels of calcium are toxic to cells and contribute to loss of neurons in Alzheimer’s disease.
- Researchers found that a protein that protects cells from elevated calcium declines with age.
- Treatments that target the protein might help prevent neurodegeneration.
...
Glyoxalase 1 (GLO1) is a protein that plays an essential role in getting rid of toxic byproducts in cells. In the study, ... researchers discovered elevated GLO1 levels in the brains of animals with excessive levels of cellular calcium, finding that the brain increased GLO1 expression as a protective mechanism to mitigate the effects of the calcium dysregulation.
However, with advancing age, GLO1 activity declined, the researchers found, which may make the brain less resilient to neurodegeneration. The study could inform the development of therapeutics that target GLO1 and prevent neurodegeneration. ..."
From the abstract:
"Alzheimer disease (AD) is characterized by plaques and tangles, including calcium dysregulation and glycated products produced by reactive carbonyl compounds. AD brains have increased glyoxalase I (GLO1), a major scavenger of inflammatory carbonyl compounds, at early, but not later, stages of disease. Calcium dysregulation includes calcium leak from phosphorylated ryanodine receptor 2 (pS2808-RyR2), seen in aged macaques and AD mouse models, but the downstream consequences of calcium leak remain unclear.
Here, we show that chronic calcium leak is associated with increased GLO1 expression and activity.
In macaques, we found age-related increases in GLO1 expression in the prefrontal cortex (PFC), correlating with pS2808-RyR2, and localized to dendrites and astrocytes. To examine the relationship between GLO1 and RyR2, we used S2808D-RyR2 mutant mice exhibiting chronic calcium leak through RyR2, and found increased GLO1 expression and activity in the PFC and hippocampus as early as 1 month and as late as 21 months of age, with a bell-shaped aging curve. These aged S2808D-RyR2 mice demonstrated impaired working memory. As with macaques, GLO1 was expressed in astrocytes and neurons.
Proteomics data generated from S2808D-RyR2 synaptosomes confirmed GLO1 upregulation. Altogether, these data suggest potential association between GLO1 and chronic calcium leak, providing resilience in early stages of aging."
Ryanodine receptor 2–mediated calcium leak is associated with increased glyoxalase I in the aging brain (open access)
Fig. 1 GLO1 expression increases with age and correlates with p-S2808-RyR2 in the rhesus macaque brain.
No comments:
Post a Comment