admin Researchers already knew that men and postmenopausal women have a higher risk of developing Parkinson’s disease than premenopausal women. Now, a recent study in mice concludes that estrogen may be responsible.
Parkinson’s disease is a neurodegenerative condition. According to the National Institutes of Health (NIH), about 50,000 people in the United States receive a diagnosis of Parkinson’s every year.
One of the primary risk factors is advanced age, so as the population grows ever older, the number of Parkinson’s cases is likely to rise.
Understanding how and why the condition develops is paramount because there is currently no cure.
The primary driver of Parkinson’s is a mutated, shorter-than-normal version of a protein called alpha-synuclein.
Although scientists have been studying Parkinson’s for decades, there are still many gaps in their knowledge.
One of these unanswered questions is why Parkinson’s occurs earlier in men and is more common in postmenopausal women.
Recently, a group of researchers from Harvard Medical School in Boston, MA, decided to take a close look at the role of estrogen. They published their findings in the journal JNeurosci.
Earlier studies identified a relationship between estrogen and Parkinson’s disease.
For instance, the authors of a 2004 study investigating Parkinson’s risk and its relationship with “reproductive characteristics” concluded that there was “[a]n association between factors reducing estrogen stimulation during life and [Parkinson’s disease].”
The Harvard researchers used a new mouse model of Parkinson’s disease that they first described in 2018. They treated the mice with DHED, a chemical that boosts estrogen levels in the brain.
The scientists chose this approach because estrogen therapy can have a negative effect on other biological systems. For instance, it increases the risk of stroke and breast cancer.
The researchers compared the motor function of male and female mice before and after treatment. They also looked at how alpha-synuclein was behaving within the brain and the rate of neuron death.
The female mice had less severe symptoms than the male mice, but estrogen treatment still improved their symptoms. In male mice, estrogen slowed the loss of nerve fibers and improved motor symptoms.
The scientists noted that estrogen reduced the buildup of mutated alpha-synuclein by boosting autophagy, which is one of the body’s mechanisms for removing cellular debris.
Among other changes, they showed that DHED treatment in male mice increased the number of nerve fibers that produce tyrosine hydroxylase — this enzyme helps convert an amino acid into L-DOPA, a precursor for dopamine. They also noted that these fibers were more abundant in female mice with or without treatment.
In combination with earlier work, these findings bolster the idea that estrogen protects against Parkinson’s disease.
They also suggest that estrogen treatment might be beneficial even after symptoms have started, which is important because spotting neurodegenerative conditions before symptoms arise is challenging.
However, as always, the transition from an animal model to clinical trials in humans will be the making or breaking of this theoretical intervention.
The researchers hope that boosting estrogen in human brains might, one day, offer a way to slow Parkinson’s disease progression.
Magazine 
