Posted on Feb 21, 2017, 6 a.m.
A calcium imbalance within the brain cell may be the cause of Alzheimer's.
Scientific research shows that an imbalance of calcium within brain cells has the potential to cause Alzheimer's disease. It appears as though this imbalance catalyzes the neurodegenerative process. Of particular importance are the mitochondria within brain cells. Mitochondria, often called the "powerhouse of the cell" are tiny structures that turn energy derived from food into fuel for cells. The mitochondria of brain cells have calcium ions that control the amount of energy produced for brain functionality.
About the Research
Pooja Jadiya led the research. He is a postdoctoral fellow that Temple University. The study was performed by Jadiya and a team of researchers at Temple's Center for Translational Medicine. Their findings were publicized in New Orleans, Louisiana at the 61st Meeting of the Biophysical Society.
How the Research was Performed
Jadiya and his team analyzed brain samples taken from Alzheimer's patients as well as a mouse model that was genetically altered to simulate the symptoms of Alzheimer's disease. A mutant cell line with Alzheimer's was also included in the study. Jadiya's team studied mitochondrial changes in the context of calcium processing along with the generation of reactive oxygen species, cell death, membrane potential and the metabolism of an active amyloid protein.
Healthy brains have calcium ions that depart neuron mitochondria to avoid an excessive buildup. The protein transporter known as the mitochondrial sodium-calcium exchanger makes this process possible. Jadiya's research team found that sodium-calcium exchanger levels were egregiously low in tissue affected by Alzheimer's disease. The protein was so low that it proved quite challenging to pinpoint. Jadiya hypothesized this phenomenon would spur an abundance of reactive oxygen species, which would result in a hastening of neurodegeneration. Also known as “ROS”, reactive oxygen species are molecules that can harm proteins, DNA and lipids when present in high levels. The result is oxidative stress.
Alzheimer's Progression Partially Hinges on the Sodium-Calcium Protein Exchanger
Jadiya's research team found a correlation between heightened neuronal death and minimized sodium-calcium exchanger activity. Mouse model data shows that the gene responsible for encoding the exchanger was much less active ahead of the onset of Alzheimer's disease. Reduced activity in this gene's expression is additional evidence that the protein exchanger plays a vital role in the disease's advancement.
The team of scientists studied this mechanism in a cell culture model affected by Alzheimer's disease by forcing heightened exchanger levels. As predicted, the affected cells recovered to the extent that they were almost indistinguishable from healthy cells. It is also worth noting that as adenosine triphosphate (ATP) levels heightened, ROS levels fell and fewer neurons died. Biologists view ATP as the energy currency for life, as the body requires it for every single activity it performs.
Why the Research Matters
Previous studies showed that an abundance of calcium spurs the death of neurons. This means there is a link between an imbalance of calcium and the neurodegenerative process that occurs when Alzheimer's disease sets in. The study outlined above is the first evidence of an exact mechanism linking mitochondrial calcium imbalance to the onset of Alzheimer's disease. This research was the first to use the array of model systems described above.
The research might set the stage for additional treatment options. The research team is now working to reverse the neurodegeneration of Alzheimer's disease by working on mouse models. They are stimulating the gene expression responsible for encoding the sodium-calcium exhanger. Such a stimulation could be accomplished with gene therapy or new drugs. The hope is that an alteration in the exchanger's activity or expression level will serve as an effective therapy that prevents the onset of Alzheimer's.
Biophysical Society. "Imbalance of calcium in a cell's energy factory may drive Alzheimer's disease." ScienceDaily. ScienceDaily, 14 February 2017.