’Lack of Cleaning’ in Brain Cells Is
Central to Alzheimer’s Disease
Scientists around the world are still struggling to understand Alzheimer's better in order to be able to treat and potentially prevent the development of the debilitating disease in the future. No new medications have been approved during recent years.
In a new study in the scientific journal Nature Neuroscience, an international team of researchers from theUniversity of Copenhagen ,
National Institutes of Health and the University of Oslo
‘When the cleaning system does not work properly, there will be an accumulation of defective mitochondria in the brain cells. And this may be really dangerous. At any rate, the poor cleaning system is markedly present in cells from both humans and animals with Alzheimer's. And when we improve the cleaning in live animals, their Alzheimer's symptoms almost disappear,’ says Vilhelm Bohr, author of the study and affiliate professor at the Center for Healthy Aging and National Institutes of Health.
Defect Energy Factories
The researchers have looked more closely at the cleaning process in brain cells from deceased Alzheimer's patients, in Alzheimer's-induced stem cells and in live mice and roundworms with Alzheimer's. In addition, they have also tested active substances targeted at the cleaning process in the animal models.
‘It significantly strengthens our results that the cleaning process seems to be important in both human cells and across different animal species. And then it is encouraging that in living animals we are able to improve the central Alzheimer's symptoms, memory and learning,’ says Vilhelm Bohr.
The mitochondria lie inside the cell and can be seen as the cell's energy factories. Mitophagy breaks down defective mitochondria and reuses the proteins that they consist of. It is known from previous research that dysfunctional mitophagy is associated with poor function and survival of nerve cells, but so far, the connection with Alzheimer's is unclear.
Slowing Down the Accumulation
In both Alzheimer's and other states of dementia, there is an accumulation of the proteins tau and beta amyloid in the brain, leading to cell death. In the new animal models, the researchers show that when boosting the mitophagy, such accumulation will slow down.
The researchers believe that altogether their findings indicate that the cleaning process is a potential target for the treatment of Alzheimer's, which should be further investigated. They therefore plan to start clinical trials in humans in the near future.
Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress. The process of mitophagy was first described over a hundred years ago by Lewis and Lewis. Ashford and Porter used electron microscopy to observe mitochondrial fragments in liver lysosomes by 1962, and a 1977 report suggested that "mitochondria develop functional alterations which would activate autophagy." The term "mitophagy" was in use by 1998.
Mitophagy is key in keeping the cell healthy. It promotes turnover of mitochondria and prevents accumulation of dysfunctional mitochondria which can lead to cellular degeneration. It is mediated by Atg32 (in yeast) and NIX and its regulator BNIP3 in mammals. Mitophagy is regulated by PINK1 and parkin proteins. In addition to the selective removal of damaged mitochondria, mitophagy is also required to adjust mitochondrial numbers to changing cellular metabolic needs, for steady-state mitochondrial turnover, and during certain cellular developmental stages, such as during cellular differentiation of red blood cells
University of Copenhagen
– February 14, 2019 -- An international research team with representation from
the University of
Copenhagen
Scientists around the world are still struggling to understand Alzheimer's better in order to be able to treat and potentially prevent the development of the debilitating disease in the future. No new medications have been approved during recent years.
In a new study in the scientific journal Nature Neuroscience, an international team of researchers from the
‘When the cleaning system does not work properly, there will be an accumulation of defective mitochondria in the brain cells. And this may be really dangerous. At any rate, the poor cleaning system is markedly present in cells from both humans and animals with Alzheimer's. And when we improve the cleaning in live animals, their Alzheimer's symptoms almost disappear,’ says Vilhelm Bohr, author of the study and affiliate professor at the Center for Healthy Aging and National Institutes of Health.
Defect Energy Factories
The researchers have looked more closely at the cleaning process in brain cells from deceased Alzheimer's patients, in Alzheimer's-induced stem cells and in live mice and roundworms with Alzheimer's. In addition, they have also tested active substances targeted at the cleaning process in the animal models.
‘It significantly strengthens our results that the cleaning process seems to be important in both human cells and across different animal species. And then it is encouraging that in living animals we are able to improve the central Alzheimer's symptoms, memory and learning,’ says Vilhelm Bohr.
The mitochondria lie inside the cell and can be seen as the cell's energy factories. Mitophagy breaks down defective mitochondria and reuses the proteins that they consist of. It is known from previous research that dysfunctional mitophagy is associated with poor function and survival of nerve cells, but so far, the connection with Alzheimer's is unclear.
Slowing Down the Accumulation
In both Alzheimer's and other states of dementia, there is an accumulation of the proteins tau and beta amyloid in the brain, leading to cell death. In the new animal models, the researchers show that when boosting the mitophagy, such accumulation will slow down.
The researchers believe that altogether their findings indicate that the cleaning process is a potential target for the treatment of Alzheimer's, which should be further investigated. They therefore plan to start clinical trials in humans in the near future.
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Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress. The process of mitophagy was first described over a hundred years ago by Lewis and Lewis. Ashford and Porter used electron microscopy to observe mitochondrial fragments in liver lysosomes by 1962, and a 1977 report suggested that "mitochondria develop functional alterations which would activate autophagy." The term "mitophagy" was in use by 1998.
Mitophagy is key in keeping the cell healthy. It promotes turnover of mitochondria and prevents accumulation of dysfunctional mitochondria which can lead to cellular degeneration. It is mediated by Atg32 (in yeast) and NIX and its regulator BNIP3 in mammals. Mitophagy is regulated by PINK1 and parkin proteins. In addition to the selective removal of damaged mitochondria, mitophagy is also required to adjust mitochondrial numbers to changing cellular metabolic needs, for steady-state mitochondrial turnover, and during certain cellular developmental stages, such as during cellular differentiation of red blood cells
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