A recent study by scientists from Northwestern University discovered that treating neurodegenerative diseases like Parkinson’s disease (PD) with antioxidants may halt degeneration and improve neuronal function, as reported by the Science Daily.
Moreover, the study, which was published in Science, found that mouse models of PD did not have the same abnormalities that were found in human PD neurons. This revealed the importance of studying human neurons to develop new therapies. (Related: Soothe Parkinson’s disease with nutritional therapy, tai chi and dancing the tango.)
PD is a chronic and progressive movement disorder, which means that symptoms continue and worsen over time. It is the second most common neurodegenerative disorder, mainly caused by the death of dopamine-containing neurons in the region of the brain the is involved in motor control called substantia nigra.
Normally, people lose dopamine neurons as they get older. However, people with PD lose more of these neurons and the remaining cells are no longer able to compensate.
In the United States, nearly one million people suffer from this disease. The primary motor signs of PD include slowness of movement, rigid limbs and trunk, impaired balance and coordination, and tremor of the hands, arms, legs, jaw, and face. Until today, there is no cure. However, there are treatment options to manage its symptoms such as medication and surgery.
Dimitri Krainc, the senior author of the study, highlighted that understanding how and why these neurons die is an important step in identifying treatments.
The research was started in 2011 in Krainc’s laboratory at Massachusetts General Hospital and Harvard Medical School and was only completed in the last four years at Feinberg.
Krainc and his team used human neurons from PD patients to identify a toxic cascade of mitochondrial and lysosomal dysfunction initiated by an accumulation of oxidized dopamine and alpha-synuclein, a type of protein also known as “Lewy Bodies.”
To be more particular, the study showed that an accumulation of oxidized dopamine impaired the activity of lysosomal glucocerebrosidase, an enzyme which is responsible for PD. This weakened the overall lysosomal function and contributed to the degeneration of neurons.
In addition, Krainc and his colleagues found that the dopamine damaged the mitochondria of the neurons by increasing mitochondrial oxidant stress, which led to the increase of oxidized dopamine levels creating a vicious cycle.
“The mitochondrial and lysosomal pathways are two critical pathways in disease development,” said Krainc, who is also the director of the Center for Rare Neurological Diseases and a professor of neurological surgery and of physiology.
He added that their study linked the major pathological features of PD, combined with the alpha-synuclein accumulation.
After the toxic cascade was catalogued, the researchers looked for ways to interrupt it.
“One of the key strategies that worked in our experiments is to treat dopamine neurons early in the toxic cascade with specific antioxidants that improve mitochondrial oxidant stress and lower oxidized dopamine,” Krainc explained.
They found that the downstream toxic effects in human dopaminergic neurons can be prevented with this kind of approach. It may provide a target for the future development of therapies.
According to Krainc, difficulties may be encountered in identifying patients with early-stage neurodegeneration because damage has often occurred far before any symptoms are apparent. Early detection will rely on brain imaging and other clinical signifiers.
Mouse models of PD did not demonstrate the same toxic cascade in human cellular models because of the differences in metabolism of dopamine between species, according to the researchers.
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