The Editor at KurzweilAI reports on research from the University of Southern California showing How chronic stress causes Alzheimer’s, other brain diseases. Scientists now think they have found the exact mechanism by which stress causes overproduction a protein called RCAN1, and how either too much, or too litlle RCAN1 may cause numerous neurodegenerative diseases, including Alzeimer's, and Huntington's, and is linked to Down Syndrome.
Chronic stress has long been linked with neurodegeneration. Scientists at the University of Southern California (USC) have now found a mechanism: chronic stress (physical or mental) causes over expression of the RCAN1 gene, in turn leading to neurodegenerative disease.
The mechanism involves these steps:
1. Chronic overproduction of RCAN1 causes hyperphosphorylation of tau proteins in the brain. (In a healthy person, the RCAN1 gene helps cells cope with stress.)
2 Tau proteins stabilize microtubules, which are like scaffolding, used to build the brain’s neurons. Previous research has shown that when the tau protein binds too much phosphate (a process called hyperphosphorylation), it forms snarls that prevent the brain’s signals from effectively traveling.
3. These neurofibrillary tangles eventually choke the life out of neurons, killing off brain function a tiny piece at a time in what is outwardly recognized as degenerative brain disease.
The researchers suggests that over expression of RCAN1 is also connected to Amyloid beta (overproduction of the Amyloid beta peptide), a competing theory of neurodegeneration. ... Further supporting the RCAN1 role are observations that it has been also shown to be chronically over expressed from birth in the brains of patients with Down syndrome. The researchers have also shown a connection between too little RCAN1 production and Huntington’s disease.
Under the fold, we will examine a more detailed paper by the original scientists.
Robert Perkins, of the University of Southern California reports that Chronic Stress Can Cause Brain Disease.
Think of a gene as a pattern or mold that generates specific proteins. For example, if 200 RCAN1 proteins are built where only 100 were needed, scientists would describe this as “overexpression” of the RCAN1 gene.
In a healthy person, the RCAN1 gene helps cells cope with stress. Overproduction, however, eventually can damage neurons, preventing the brain’s signals from traveling and causing disease. Chronic overproduction of RCAN1 causes hyperphosphorylation of tau proteins in the brain.
Tau proteins stabilize microtubules, which are like the scaffolding used to build the brain’s neurons. Previous research has shown that when the tau protein binds too much phosphate - a process called hyperphosphorylation - it forms snarls that prevent the brain’s signals from effectively traveling.
“One can imagine that it becomes sticky and makes tangled scaffolding,” Davies said. These neurofibrillary tangles eventually choke the life out of neurons, killing off brain function a tiny piece at a time in what is outwardly recognized as degenerative brain disease.
Currently, there are two competing theories about the leading cause of neurodegeneration in Alzheimer’s disease: overproduction of the Amyloid beta peptide and tau hyperphosphorylation. Research in the Davies lab suggests that overexpression of RCAN1 is connected to both and appears to unite the Amyloid beta and tau theories of neurodegeneration.
And, surprisingly, the authors apparently find that RCAN1 also plays a role in "RCAN1 has been shown to be chronically overexpressed from birth in the brains of patients with Down syndrome."
Davies’ lab also has shown a connection between too little RCAN1 production and Huntington’s disease. “Our results suggest that the cellular levels of RCAN1 proteins must be kept within a fairly narrow range in order to avoid serious dysfunction,” Davies said.
For anyone suffering from these devastating brain diseases and their loved ones, this research provides some hope that our understanding of how they development may lead to ways to prevent them, or prevent further progression.
In the meantime, fellow Kossacks, take care of yourselves, avoid stress, and relax. Or, as my son says "Chill-lax." I asked him if he had in "chill-laxatives.
How ever you do it stay calm and avoid excess stress.
And, have a fun and safe Fourth of July weekend.
Ref.: K. J. A. Davies, et al., Do RCAN1 proteins link chronic stress with neurodegeneration? The FASEB Journal, 2011; [DOI: 10.1096/fj.11-185728]