The stress hormone cortisol prevents dopaminergic neurons from dying by promoting the expression of parkin, a protein that is in short supply in the brains of Parkinson’s disease patients, a study indicates.
The research, “Hydrocortisone-Induced Parkin Prevents Dopaminergic Cell Death Via CREB Pathway In Parkinson’s Disease Model,” was published in the journal Scientific Reports.
“Our results showed that [cortisol] could stimulate parkin expression via [a survival] pathway and the induced parkin expression was accountable for its neuroprotective effect,” researchers wrote. Expression is the process by which information from a gene is used to create a functional product, like a protein.
“Since glucocorticoid [corticoid] is a physiological hormone, maintaining optimal levels of glucocorticoid might be a potential therapeutic or preventive strategy for Parkinson’s disease,” the researchers added.
Symptoms of Parkinson’s, such as tremors and movement problems, result from the death of dopaminergic neurons in the brain, particularly in a region called the substantia nigra. Mutations in the parkin protein are known to contribute to this effect.
Previous studies have shown that promoting parkin expression protects against cell stress and prevents dopamine cell loss. The research was done in several animal models of Parkinson’s.
In the latest study, researchers used molecular screening to identify chemicals that increase parkin expression. They found that cortisol can trigger parkin expression and protect cells against oxidative stress, or damage to cell molecules from high levels of oxidant molecules.
Cortisol increased parkin levels in the brains of mice and prevented dopamine cell loss after four days.
An obstacle to using cortisol to prevent neuron loss is its side effects, researchers said. They include suppression of the immune system, high levels of blood glucose and amino acids, a rise in blood pressure, and psychosis, a mental disorder that actually may damage the brain.
“The dosage of hydrocortisone used to provide complete protection to dopaminergic neurons in our study was low compared to its dosage used to suppress immune response (0.4 mg/kg in our study vs. 20–100 mg/kg for anti-inflammatory effects in other studies),” the researchers wrote. “Based on our findings, it would be critical to have sufficient physiological supply of cortisol hormone … for protection of the brain. In this respect, hydrocortisone treatment could be considered as a supplementary measure to maintain parkin expression without causing serious side effects.”
“The significance of this study is that it has identified that the expression of parkin protein induced by a moderate level of the stress hormone cortisol could be an important factor in maintaining the viability of dopaminergic neurons,” Yoon-Il Lee, the study’s senior author, said in a news release. “We will continue to conduct follow-up studies such as clinical studies so that Parkinson’s disease will be curable in the future.”
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