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SFS - Parkinson's Disease II


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Does PD get worse with aging?
Causes of PD?
Environmental toxins - rural farming, well water, chemicals
Oxidative stress
Genetic factors
What % of PD worldwide is genetic?
Essay....Why would L-dopa cause vomiting?
L-dopa is converted to DA in the periphery, which stimulates the area postrema (vomiting center).
Gold standard for PD treatment?
PD is the likely result of what 2 factors?
genetic predisposition and environmental exposure
In Park 1, a single nucleotide change occurs in what protein found in Lewy bodies of PD patients?
alpha-synuclein (may be involved in trafficking of DA vesicles)
Explain the rural hypothesis of PD onset.
Pesticides and herbicides in large concentrations in well water, could set off an already existing genetic predisposition for PD.
PD can result from destruction/damage to what resulting in substantia nigra and locus ceruleus cell death?
By bacteria going after the proteosome or MPTP going after the mitochondria of these cells.
Describe oxidative stress theory.
Chemicals can cause cascade of bad things...causative factors are MPTP and dopamine.
General mechanism of MPTP.
Found in a synthetic demerol. MPTP crosses the BBB, and completely destroys the substantia nigra resulting in PD symptoms.
Chemicals useful in creating animal models for PD.
Reserpine and MPTP
MPTP is taken up by what type of cell?
astrocytes. Astrocytes convert MPTP to MPP+(toxic) with MAO-B (inhibitors of MAO-B may help PD).
What is the toxic compound of MPTP action?
MPP+. DA transporter mistakes it as DA and takes it into the cell, poisoning the mitochondria.
What enzyme is missing in PD patients that typically neutralizes hydrogen peroxide from DA breakdown?
Cause DNA damage, Ca++ entry into cell, and lipid memb. breakdown.
hydroxyl free radicals. Activate degradative enzymes dissolving cell from inside out.
________ are formed by an accumulation of mutated alpha-synuclein.
Lewy bodies. In PD, the cell can't get rid of synuclein.
Result of a non-functional or absent proteosome.
Build-up of undesired proteins in the cell. Lewy body as well.
A chemical used by the mitochondrion in the ETC that can slow PD progression by 30%.
Coenzyme Q10
Can "bring cells back to life" but can't cross BBB.
Glial-derived neurotrophic factor.
Ideas in PD gene therapy.
Blocking GABA, increasing tyrosine hydroxylase (or DA), and GDNF.
Deep brain stimulation here will improve symptoms for what condition(s)?
a. Vim
b. Gpi
c. STN
a. tremor
b. dystonia
c. Parkinson's symptoms
Why aren't pallidotomies and thalamotomies ideal?
The lesions will heal, causing symptoms to return. Also, if done bilaterally will cause side effect profile to go up.
Did adrenal gland transplants for PD work?
Did DA-producing fibroblasts?
Um...NO and NO.
Side effect of using fetal stem cells for PD.
Produced "off" dyskinesia in absence of L-dopa treatment. (From scripts) this seems like it is "on" and "off" symptoms...rigidity and immobility paired with chorea.
Excessive amounts of L-dopa can cause what?
ON dyskinesia.
Therapy using DA-producing retinal epithelial cells grown on plastic beads injected into the brain.
Number of contacts in the STN for deep brain stimulation.

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