Small ion and large problem - calcium and alzheimer's disease
Alzheimer disease (AD) is one of the most common forms of dementia associated with age. It affects millions of people world-wide and there is no treatment to stop or delay its progress. The major risk factor of AD is age: statistically for 90 years old people every second will be affected. Because of a longer lifespan the number of AD patients is increasing. The disease lasts long and is devastating not only for patients, but also for the family members, who have to take 24 h care of them at later stages of the disease. All clinical trials based on the current AD hypotheses failed and some researchers predict that targeting metabolism of beta-amyloid is not the promising path to cure the disease. Thus, there is an increasing interest in searching for new potential drug targets in AD: proteins of calcium homeostasis represent some of them. Calcium signaling regulates multiple neuronal functions including synaptic transmission, plasticity and cell survival. Dysregulation of calcium homeostasis undergoes subtle changes during physiological ageing and affects neuronal function and survival. At the cellular level calcium buffering impairment, alterations in calcium entry routes into neurons, as well as mitochondrial and endoplasmic reticulum dysfunctions are observed in AD models. One of the possible targets of dysregulated calcium homeostasis in AD are proteins involved in store operated calcium entry (SOCE): Orai, calcium channel forming protein in plasma membrane and calcium sensors STIMs, located in ER. The understanding of neuronal mechanism of SOCE might help to explain the impairment of calcium homeostasis observed in AD. To identify potential drugs allowing restoring calcium homeostasis the high throughput screens are needed. We developed such screen (Honarnejad et al., abstract on AD/PD2011), which was applied to identify compounds affecting cellular calcium concentration.
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