Appoptosin is a killer of neurons
The connection between the protein appoptosin and the death of neurons during neurodegeneration has been established
LifeSciencesToday by Sanford-Burnham Medical Research Institute: Hunting neuron killers in Alzheimer's and TBIScientists at the Sanford-Burnham Medical Research Institute have established the role of the appoptosin protein
(appoptosin) in the induction of the process of "suicide" of neurons in a number of neurological diseases. The protein appoptosin may become a target of new drugs for the treatment of Alzheimer's disease and traumatic brain injuries.
Cognitive disorders and memory loss in patients with neurodegenerative diseases, such as Alzheimer's disease, and traumatic brain injuries are caused by the death of neurons, the main causes of which scientists need to understand first of all in order to better diagnose and treat these neurological diseases.
Professor of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at Sandford-Burnham Huaxi Xu, PhD, and his group have been studying the protein apoptosin and its role in the development of neurodegenerative diseases for the past few years. The levels of apoptosin in the brain are rapidly increasing in diseases such as Alzheimer's disease and stroke, and this increase is most pronounced after traumatic brain injuries.
Appoptosin is known for its participation in the synthesis of heme, a molecule that carries iron (remember hemoglobin, which gives red color to our blood). But what does a heme have in common with dying brain cells? As Dr. Xu and his colleagues explain in their article published in The Journal of Neuroscience (Zhang et al., Appoptosin is a Novel Pro-Apoptotic Protein and Mediates Cell Death in Neurodegeneration), excess heme leads to supersynthesis of reactive oxygen species – cell–destroying radicals and peroxides – and apoptosis - strictly regulated the process of programmed cell death. This means that the cause of neuronal death is an excess of apoptosin and an excess of heme.
In brain samples of patients with Alzheimer's disease and heart attack and rodents with a stroke model, as well as in neurons treated with beta-amyloid and glutamate, the levels of the protein appoptosin interacting with the beta-amyloid precursor protein (APP) are increased. Apoptosin induces the formation of reactive oxygen species and caspase-dependent apoptosis of neurons (red). (Photo: Sanford-Burnham Medical Research Institute)
Professor Xu and his group not only deciphered the neurodegeneration mechanism mediated by appoptosin and heme, but also made a very important observation: suppression of appoptosin in laboratory cell cultures prevents cell death. This fact suggests that appoptosin is a promising new target of drugs for the treatment of neurodegenerative diseases.
Now scientists are studying the functions of apoptosin in mouse models and are looking for new treatments that will target this protein.
"Since in diseases such as Alzheimer's disease, an important role in cell death is played by a violation of the regulation of apoptosin, we are looking for small molecules that modulate its expression or activity. Then we will determine whether these compounds can be potential drugs for the treatment of Alzheimer's disease and other neurodegenerative diseases," explains Dr. Xu.
However, slowing down the out-of–control expression of apoptosin is not an easy task. First of all, because we still need this heme-forming protein to function at a normal level and our blood to carry iron. In one of the previous studies, it was found that a mutation in the gene encoding apoptosin leads to the development of anemia.
"Too much of anything is bad, but it's bad and too little," says Professor Xu.
New methods of treatment of neurodegenerative diseases and traumatic brain injuries are urgently needed. According to Centers for Disease Control and Prevention (CDC), about 1.7 million U.S. residents receive traumatic brain injuries every year. This is an acute condition, but it can also lead to long–term consequences - epilepsy and an increased risk of developing Alzheimer's and Parkinson's diseases.
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