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 overexpression 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 overexpression 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 overexpressed from birth in the brains of patients with Down syndrome. These patients develop neurofibrillary tangles and typically start to experience the onset of Alzheimer’s disease around age 40. The researchers have also shown a connection between too little RCAN1 production and Huntington’s disease.

USC teamed up with scientists from Monash University of Australia and the Institute of Nuclear Sciences in Serbia on this study.

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]