Your doctor should have you well versed in prevention of Parkinsons already. But better to
be prepared without them. I'm doing everything possible not to get this
since my Dad has it.
14 posts on Parkinsons prevention here.
Ask your doctor which one of these will guarantee not getting Parkinsons, that is a non-negotiable question.
Should we have it cut?
The latest here: What does your doctor prescribe to prevent Parkinsons?
Northwestern
Medicine scientists have identified a toxic cascade that leads to
neuronal degeneration in patients with Parkinson's disease (PD) and
figured out how to interrupt it, reports a study published September 7
in the journal Science.
Intervening with an antioxidant early in the disease process may
break the degenerative cycle and improve neuron function in PD, the
study showed.
The scientists also discovered that mouse models of PD didn't have
the same abnormalities they found in human PD neurons, revealing the
importance of studying human neurons to develop new therapies.
Dr. Dimitri Krainc, the Aaron Montgomery Ward Professor and chair of
neurology at Northwestern University Feinberg School of Medicine, is the
study senior author. Lena Burbulla, a postdoctoral fellow in Krainc's
laboratory, is first author.
The research was started about six years ago in Krainc's lab at
Massachusetts General Hospital and Harvard Medical School and was
completed in the last four years at Feinberg.
PD is the second most common neurodegenerative disorder, primarily
caused by the death of dopamine-containing neurons in the substantia
nigra, a region of the brain involved in motor control. While people
naturally lose dopamine neurons as they age, patients with PD lose a
much larger number of these neurons and the remaining cells are no
longer able to compensate.
Understanding how and why these neurons die is an important step in
identifying treatments, Krainc said. While previous research indicated
that the cellular mechanism behind the cell death involved the
mitochondria and lysosomes, how these two pathways converge in dopamine
neurons to cause cell death remained unknown up until now.
Using human neurons from Parkinson's patients, Krainc and colleagues
identified a toxic cascade of mitochondrial and lysosomal dysfunction
initiated by an accumulation of oxidized dopamine and a protein called
alpha-synuclein. Specifically, the current study demonstrated that an
accumulation of oxidized dopamine depressed the activity of lysosomal
glucocerebrosidase (GCase), an enzyme implicated in PD. That depression
in turn weakened overall lysosomal function and contributed to
degeneration of neurons.
The accretion of oxidized dopamine didn't just interfere with
lysosomes, however. Krainc and his colleagues discovered that the
dopamine also damaged the neurons' mitochondria by increasing
mitochondrial oxidant stress. These dysfunctional mitochondria led to
increased oxidized dopamine levels, creating a vicious cycle.
"The mitochondrial and lysosomal pathways are two critical pathways
in disease development," said Krainc, who also is the director of the
Center for Rare Neurological Diseases and a professor of neurological
surgery and of physiology. "Combined with the alpha-synuclein
accumulation, this study links the major pathological features of PD."
Once they had catalogued this toxic cascade, Krainc and his colleagues began looking 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 said. "With this approach, we found that we can attenuate or
prevent the downstream toxic effects in human dopaminergic neurons."
This approach to interrupting the toxic cascade of oxidized dopamine
may provide a target for the development of future therapies. However,
identifying patients or subjects with early-stage neurodegeneration can
be difficult, because damage has often occurred far before any symptoms
are apparent, according to Krainc.
Consequently, genetic testing will be central to future diagnostic
efforts. Causative genes are prime candidates for screening, while risk
genes such as GBA1 are less conclusive but still important markers,
Krainc said. Early detection will also rely on brain imaging and other
clinical signifiers.
Interestingly, when compared to human cellular models, mouse models
of PD did not demonstrate the same toxic cascade, according to the
study. Krainc and his colleagues showed this is due to differences in
metabolism of dopamine between species, and underscored the importance
of studying human neurons to discover new targets for drug development.
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