An international study led by the Laboratory of Molecular Physiology at Pompeu Fabra University (UPF) in barcelona identified new genes that modulate the toxicity of the ß-amyloid protein, responsible for causing Alzheimer’s disease.
Combining molecular biology, genomics and bioinformatics techniques, the researchers identified 238 genes protectors or activators against Alzheimer’s disease.
Among them, the Surf4 gene stands out, which is involved in the control of intracellular calcium and, by increasing ß-amyloid protein toxicity, it contributes to diseaseresponsible for seven out of ten cases of dementia in the world, where 10 million new cases are diagnosed each year.
Alzheimer’s disease develops with age, when ß-amyloid protein, a small protein secreted by neurons, begins to unfold and clump together inside the brain, becoming a neurotoxic effectcurrently there is no effective treatment to prevent the aggregation and neurotoxicity of this protein.
This work, published in the ‘International Journal of Molecular Sciences’, identified 238 genes in yeastsimilar to those in humans, which regulate Alzheimer’s disease.
Of these, 81 enhance ß-amyloid protein toxicity and 157 are protective against this cellular toxicity.
Using bioinformatics analysis, the researchers saw this more of the 238 identified genes They are involved in mitochondrial activity, protein translation and regulation of intracellular calcium.
In this last process, where most of the identified genes are involvedhighlights the Surf4 gene, whose protein regulates the entry of calcium into the cell and has been shown to increase the toxicity of the ß-amyloid protein, contributing to Alzheimer’s disease.
As explained by the study coordinator, Francisco J. Muñoz, “Calcium is one of the most important messengers that carry information from outside in the cells. It’s involved in almost every cellular function.”
“That’s why -he specified- when the Surf4 protein is overexpressed, which prevents the entry of calcium and aborts the cellular processes that depend on it, neurons cannot function and become very sensitive to amyloid toxicity.”
According to the researcher, the identification of SURF4 as an accelerator of damage by ß-amyloid protein toxicity opens doors to identify new therapeutic targets that regulate amyloid toxicity in Alzheimer’s disease.
To identify the genes that regulate Alzheimer’s disease, researchers analyzed a collection of 5,154 mutants of the yeast ‘Saccharomyces cerevisiae’ -which bears great resemblance to the human genome- from which the expression of a gene has been eliminated.
Each of these mutants was crossed with other yeasts of the same strain. that overexpress human ß-amyloid protein and analyzed the viability of these cells for several days.