How Animal Research Is Helping Scientists Understand and Treat Parkinson’s Disease
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Parkinson’s disease is a disorder of the brain and central nervous system that can cause tremors, stiffness, movement and balance issues, and cognitive impairment. Almost one million people in the U.S. are currently living with Parkinson's disease, about 50 percent more men than women.
Parkinson's disease occurs when specific nerve cells in the brain—those that produce the chemical dopamine—become damaged or die. When enough of these cells die or stop functioning correctly, the resulting drop in dopamine production causes the movement and cognitive problems associated with Parkinson's.
Since 1817, when Parkinson's disease was first officially described by James Parkinson (though descriptions of Parkinson’s-like symptoms date back to around 1,000 B.C.), scientists have been trying to pinpoint how Parkinson’s develops and find effective treatments for its debilitating symptoms. New research in mice is providing some promising answers.
Identifying the Specific Neural Pathways That Cause Parkinson’s
While it’s clear the death of certain brain cells causes the onset of Parkinson’s, the role played by specific brain circuits in causing the symptoms of Parkinson’s is not yet well understood.
A recent mouse study by researchers at the University of California, San Diego may shed some light on the relationship between neural circuits in the brain and the cognitive and motor abilities typically affected by Parkinson’s disease.
The scientists studied two regions of the external globus pallidus (GPe) in the brains of mice, an area known to be related to the motor and cognitive symptoms of Parkinson’s. By manipulating neurons in these two parts of the GPe, the research team was able to influence motor skills and learning in the mice, which led them to identify that two specific neural pathways are associated with the motor function issues and cognitive decline that are the hallmarks of Parkinson’s.
The discovery may lead to targeted treatments using those neural pathways to alleviate specific symptoms of Parkinson’s disease.
Regenerating Dopamine-Producing Cells
If Parkinson’s symptoms are caused by a lack of dopamine due to cell death, it makes sense to try to find a way to keep those dopamine-producing cells healthy. A team of researchers at Guangzhou Medical University is doing just that.
In mouse models of Parkinson’s, the team used 4,4-dimethoxychalcone (DMC) to protect and promote regeneration in cells in the brain, with the help of rabies virus glycoprotein (RVG), a molecule that is able to cross the blood-brain barrier.
When given the DMC-RVG compound, the Parkinson’s mice showed reduced neuron loss and increased dopamine production, which led to an improvement in motor function. The team hopes to move to clinical trials soon.
Preventing Alpha-Synuclein Protein Buildup
The aggregation of alpha-synuclein in the brain is a key feature of Parkinson’s disease. Now, research with mice at Johns Hopkins University has found a way to reduce the build-up of alpha-synuclein protein: treatment with the antioxidant metal-alloy nanozyme, a metal alloy made of platinum and copper called PtCu bimetallic nanoalloy (PtCuNA).
Oxidative stress—an imbalance in the production of reactive oxygen species (ROS)—is one known cause of aggregation. This imbalance can cause cell and tissue damage, and increases with age. PtCu-NAs behave like two naturally-occurring enzymes—catalase and superoxide dismutase—that break down ROSs.
In tests with mice, PtCuNAs significantly decreased ROS production and reduced aggregated protein, which could lead to a treatment to prevent alpha-synuclein aggregation in humans with Parkinson’s disease.
A Protein That Can Slow or Stop Parkinson’s
At Ben-Gurion University in Israel, researchers have found that bone morphogenetic proteins 5 and 7 (BMP5/7) can protect the neurons of mice against the accumulation of alpha-synuclein proteins.
In a mouse model of Parkinson’s, BMP5/7 was able to prevent movement impairments due to alpha-synuclein aggregation and reverse the loss of dopamine-producing brain cells.
The findings suggest that BMP5/7 could slow or stop Parkinson’s disease progression. The team is now working toward clinical testing of the discovery.
A Protein that Creates New Neurons in Mice
While some Parkinson’s researchers are focused on finding ways to prevent cell death, a team at University of California, San Diego has discovered a way to actually create new brain cells.
The catalyst for new cell growth is a protein called PTB, which influences the genes within a cell and determines whether that cell becomes a neuron or a different type of cell. The team found that when PTB was suppressed in the brains of lab mice, some of the cells in the brains of the mice were converted into dopamine-producing neurons. The increase in dopamine caused the mice to stop showing motor-related symptoms of Parkinson’s.
The team is conducting further testing to determine whether the PTB-blocking method is safe, but if the treatment can be used in humans it might lead to treatments not only for Parkinson’s but also other conditions that involve neuron death, such as Alzheimer's, Huntington’s, and stroke.
Dietary Supplement Reduces Cognitive Impairment from Parkinson’s
A team of researchers in China and Japan has found that silibinin—an extract of the milk thistle plant that is sold as an over-the-counter dietary supplement for liver conditions—can reduce cognitive impairment in a mouse model of Parkinson’s disease.
Previous mouse studies have demonstrated silibinin’s ability to reduce motor symptoms in a mouse model of Parkinson’s disease, and now it appears it can protect against cognitive decline as well.
In preclinical testing, silibinin reduced alpha-synuclein accumulation, mitochondrial impairment, and oxidative stress, all of which are features of Parkinson’s. The effects of silibinin were similar to those of memantine, which is an approved drug treatment for Alzheimer’s and is sometimes used off-label to treat dementia due to Parkinson’s.
Silibinin treatment not only lessens cognitive impairment in mouse models of Parkinson’s, it significantly reduces nerve cell damage and loss, which shows promise for a new treatment in humans that targets both cognitive and motor aspects of the disease.
With teams of researchers all over the world finding ways to treat and even reverse the effects of Parkinson’s disease, there is hope that one day soon this heartbreaking disease will be a thing of the past.