Taking Out the Trash
Taking out the trash is definitely a priority if you would like your home to smell clean and fresh. Although you may have to pinch your nose when you are throwing those sweaty gym socks in the laundry, you still manage to flush the dingy particles from the cloth in order to preserve the integrity of the socks. What you may not be aware of is that your brain may require a similar process to remain healthy.
With an aging population almost bursting at the seams, understanding the brain’s reaction to certain stimulation and lack of stimulation has become increasingly more important. The impact of neurodegenerative disorders affecting the population has sparked more profound research in tracking, mapping, and deciphering when, where, and how messages are carried throughout the brain’s intricate network.
Dr. Leonard Guarente has spent years researching genes related to the longevity of life. He is also responsible for discovering the longevity-boosting properties in SIRT1, an enzyme responsible for altering the proteins that contribute to cellular regulation, as in longevity and reaction to certain stressors. It appears that SIRT1 not only has properties that fight diseases associated with aging, but also assists in controlling the circadian rhythms in the human body. This supports the theory of the connection between sleep and the aging process.
Interestingly, studies continue to evidence the neuronal damage that can be caused by the clustering of toxic proteins in the brain. It appears the primary culprit of this action is associated with misfolded protein in plaques and neuronal inclusions. A number of unconnected diseases, including cancer, diabetes, and transmissible spongiform encephalopathies (TSEs) or prion diseases, have the pathological characteristic of deposits left by aggregated, misfolded protein.
The abnormally shaped or misfolded proteins may be responsible for killing and damaging other brain cells near where they accumulate. It is believed that in normal circumstances, brain cells recognize the mutated proteins and ‘trash them’ through the proteostasis process. This in turn controls the quality and levels of protein in the brain.
A study conducted by the University of California and Duke University using the huntingtin protein, evidenced that the rate of proteostasis may be the key to understanding, and perhaps overcoming, the neuronal damage caused by these misfolded proteins. The research indicates that the mean lifetime of the protein in a set of striatal neurons ranged from three to four fold. This would indicate that although the proteins may be the same, cells might process some slower than others.
The discovery sparked yet another test requiring the activation of the Nrf2 protein that regulates protein processing. The result indicated that the neuron had a longer life span and the huntingtin mean lifetime was shorter. The research also indicated that the cortical neurons recognized and disposed of the mutant proteins more effectively than the striatal neurons.
As striatal neurons are more susceptible to cell death than cortical neurons, this information is crucial to furthering the studies of neuronal damage associated with misfolded proteins. The discovery, as it relates to the impact these toxic and damaged proteins have in causing neurodegeneration, may be a direct result of their obstruction of the proteostasis process.
In essence, when the brain is cluttered with damaged proteins, it affects the processes of the healthy brain cells. It would be much like attempting to dispose of the kitchen garbage when the can is over-filled. As you are carrying out the trashcan, it can brush against clean objects on the way out the door. Now the disposal process will take longer. The trash will still be out of the house but the process has affected other areas in the kitchen. As is the case of an overfilled trash can, it seems that the inability of the brain to dispose of damaged proteins can cause neurodegenerative diseases.
Taylor, J. P., Hardy, J., & Fischbeck, K. (2002). Toxic proteins in neurodegenerative disease. Science, 296(5575), 1991-1995. doi: 10.1126/science.1067122
Tsvetkov AS, Arrasate M, Barmada S, Ando DM, Sharma P, Shaby BA, & Finkbeiner S (2013). Proteostasis of polyglutamine varies among neurons and predicts neurodegeneration. Nature chemical biology, 9 (9), 586-92 PMID: 23873212