Exercise vs Parkinson’s Disease

Want to hear some good news? I thought so. There’s solid evidence that regular exercise can reduce your risk of developing Parkinson’s Disease (PD) or at least slow its progression.?

About nine months before you were born, a gazillion of your father’s sperm swam blindly towards an unsuspecting egg. (Stick with me for a bit, I promise we’ll get back to PD) The egg itself was one of many millions that could have been floating down your mother’s fallopian tube. They met. They merged. The result was your unique DNA, never before and never again to be seen in this universe. You had no control over how the deck was shuffled or the genetic hand you were dealt.?

Well, you can’t trade in your DNA. But you may have some control over which of the myriad genes that are ensconced in each of your brain cells are expressed. Many of your genes come with an on/off switch. If a gene is turned on, it will make a protein. That protein will have some effect on your cell and, ultimately, your overall health. If a gene is turned off, it will remain silent. If the gene is silenced, even if you have the DNA code to make a protein, it won’t be made. The process of gene regulation is called epigenetics.?

Not only can exercise change your brain DNA, but your kids may inherit the changes. We all want to bequeath our best possible genes to the next generation and the good news is that some epigenetic changes may be heritable.

Before any prospective genetic changes can occur, they must get past the gatekeeper of the brain. There’s a delicate balance in your brain that depends upon which genes are turned on or off. Genes must be activated to produce proteins within the neurons and then deactivated before they produce too much. Your brain cells have mechanisms to regulate the activity of neuronal DNA. One gatekeeper molecule, that controls whether genes actively produce protein, is called Restrictive Element 1-Silencing Transcription factor (REST). REST, a master regulator with its hand on the on/off switch, fine-tunes brain DNA. Thus, REST is critical for proper brain development and function.

Higher cognitive functions, such as learning and memory, depend on the proper functioning of REST. If REST works properly the brain is able to overcome life’s stresses through neuroplasticity (the ability of brain cells and wiring to grow and change) and detoxification. If REST malfunctions, the brain is liable to be overrun by problems, such as accumulation of toxic proteins (like β-amyloid).? If the process breaks down your brain function may suffer and you may even develop progressive neurodegenerative disorders and diseases (including stroke (cerebrovascular accident), AD, Parkinson’s Disease (PD) and Huntington's disease).

Whether or not your brain ages normally may also depend on REST. An error catastrophe may occur if there is a bad REST malfunction; the protein balance in brain cells gets too out of whack. The neurons may be overwhelmed by oxidative stress and protein toxicity. This may cause the brain to age prematurely. Researchers are working on drugs that target REST with the hope of preserving brain function as you age or even reverse age-related brain declines (senility or dementia).

You don’t need to wait for a new drug to improve your genes. If you’re not satisfied with the DNA you were born with, you may have the power to change that! REST function is not set in stone. By improving your diet and lifestyle, you may affect REST function and thus which genes are turned on and off. Regular exercise may modify gene expression in your neurons, delaying the cognitive and memory decline of aging and preventing brain degenerative disease (such as AD and PD).

Certain DNA sequences may be especially amenable to epigenetic alteration: for example, APOE ε4. Apolipoprotein E (APOE) is a protein involved in the metabolism of fats in the body of mammals. Certain subtypes have been associated with neurodegenerative disease.?

About one quarter of PD patients may have a genetic variant called APOE ε4. (See, I told you we’d get to PD and exercise) A recent study by South Korean researchers has provided evidence that the APOE ε4 Parkinson’s disease patients may have the power to help themselves. In these particular PD patients, regular exercise may alter which segments of DNA (which genes) become activated. The research demonstrated that exercise may prevent or mitigate motor and cognitive decline (problems moving and thinking). The epigenetic alteration induced by exercise may be responsible for the increased production of BDNF in certain patients.

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