Nearly six million Americans currently live with Alzheimer’s disease (AD), with the figure set to climb to 13.8 million by 2050. And with promising trials failing close to the finish line, researchers are desperate for any breakthroughs that will lead to halting the devastating neurodegenerative disease.
The latest findings are from an international team of researchers out of Spain, whose cell study of more than 5,000 mutated yeast samples uncovered 238 genes involved in the regulation of AD.
In the study led by Barcelona’s Universitat Pompeu Fabra (UPF) Molecular Physiology Laboratory, the 238 genes linked to AD were involved in mitochondrial activity, protein translation and intracellular calcium regulation. But it was one gene in the latter functional group that stood out.
Known as Surf4, the gene’s protein regulates the entry of calcium into cells and has been shown to increase amyloid beta protein toxicity, which is believed to be a hallmark of AD degeneration. Its overactivity disrupted the ability for calcium messaging to travel between cells and accelerated the toxicity of amyloid beta.
It was one of 81 genes that were involved with increasing amyloid beta toxicity, while the other 157 identified were protective against this cellular damage.
“Calcium is one of the most important messengers that transfer information from the outside to within cells,” said study coordinator Francisco J. Muñoz from UFP. “It is involved in almost all cell functions. Hence, when the Surf4 protein is overexpressed, which decreases calcium entry and aborts the cellular processes dependent on it, neurons cannot function and they become very sensitive to amyloid toxicity.”
It’s not the first time calcium regulation has been thought to play a role in interrupting neuron pathways, with it also linked to cell death and neurodegeneration. Calcium is one of the most important intracellular messengers and is vital for cell function, especially in neurons thanks to its role in neurotransmission.
The team hopes this genetic picture will open the door to much-needed new avenues of research.
The study was published in the International Journal of Molecular Sciences.