Scientists have identified a protein that seems to be key to the processes that lead to Parkinson's disease, and is involved in the brain's response to addictive drugs like methamphetamine.
Telling that this protein is called organic cation transporter 3 (oct3), the researchers at Columbia University Medical Center and the University of Rochester Medical Center have revealed that their work fills a longstanding gap in scientists' understanding of the brain damage that causes symptoms like tremor, stiffness, slowness of movement and postural instability.
AdvertisementThe researchers have found that oct3, which shepherds molecules into and out of cells, plays a critical role by bringing toxic chemicals to the doorstep of the brain cells that die in patients with Parkinson's disease.
They have also shown that oct3 is involved in the brain's response to methamphetamine and other addictive drugs.
According to them, their study supports a role for astrocytes, a type of brain cells that has been often overlooked by scientists focused more on cells known as neurons that send electrical signals.
"Astrocytes are definitely much more than support cells in the brain. Scientists are discovering their involvement in many diseases. The latest results point to their role in Parkinson's disease," said Dr. Kim Tieu, assistant professor in the Department of Environmental Medicine at the University of Rochester Medical Center.
Tieu, who initiated the study as a post-doctoral research associate in the laboratory of Dr. Serge Przedborski, the Page and William Black Professor of Neurology at Columbia University, has revealed that they chose to study how the brain handles a chemical known as MPTP, which ultimately damages the exact same brain cells that are injured in patients with Parkinson's disease.
While MPTP does not cause Parkinson's disease, scientists regularly use it as a model for the disease because it causes an identical type of brain damage.
In the brain, this chemical is known to convert primarily in astrocytes to a chemical called MPP+, which is deadly to dopamine neurons.
An over two-decade-old study suggests that MPP+ is released from astrocytes before it kills dopaminergic neurons, but exactly how it is freed from astrocytes has been a mystery.
The current study has now shown that oct3 as the shepherd that escorts toxic MPP+ out of the astrocytes and into the space surrounding dopamine neurons, which is where another molecule known as the dopamine transporter picks it up and brings it into the neuron itself.
Upon blocking or genetically removing oct3 in mice, the researchers found that the dopamine neurons in the brains did not die despite the presence of MPTP in the brain. When oct3 was present in the usual amounts, dopamine neurons died as expected.
"The neurons affected in Parkinson's disease don't live in isolation in the brain. You must understand the brain environment as a whole to understand disease. For many years, people had a neuron-centric view of neurodegenerative diseases. But more and more scientists are realizing that if you wish to understand the process of neurodegeneration, you must take into account the astrocytes, the microglia, as well as the neurons. Astrocytes maintain an intimate relationship with neurons, and to understand one, you have to understand the other," said Przedborski.
Analysing brain tissue from people who died of Parkinson's disease, the researchers found oct3 to be active in astrocytes in the brain region affected by Parkinson's disease.
The team found the same while experimenting on mice, where the absence of oct3 correlated exactly to areas of the brain where neurons were not damaged.
The finding that oct3 may play a role matches other scientists' observations that people in whom its activity is reduced have a higher potential for addiction.
The researchers believe that the molecule may also offer a new target for treating depression. Since one of oct3's functions is to remove serotonin from the brain, blocking it may offer a new avenue to treat depression.
A research paper based on their study has been published in the online edition of the Proceedings of the National Academy of Sciences.
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