"For achieving neuroprotection and neurorescue in early clinical
parkinsonian stages, a cocktail therapy of multiple neuroprotective
agents may be more effective than the current treatment with extremely
high doses of a single antioxidative agent."
That would be a .. salad.
Neuroprotective strategies in Parkinson's disease: protection against
progressive nigral damage induced by free radicals.
Chiueh CC, Andoh T, Lai AR, Lai E, Krishna G
Neurotox Res 2000 May; 2(2-3):293-310.
Brain undergoes neurodegeneration when excess free radicals overwhelm
antioxidative defense systems during senescence, head trauma and/or
neurotoxic insults.
A site-specific ac***ulation of ferrous citrate-iron complexes in the
substantia nigra dopaminergic neurons could lead to exaggerated
dopamine turnover, dopamine auto-oxidation, free radical generation,
and oxidant stress.
Eventually, this iron-catalyzed dopamine auto-oxidation results in the
ac***ulation of neuromelanin, a progressive loss of nigral neurons,
and the development of Parkinson's disease when brain dopamine
depletion is greater than 80%.
Emerging evidence indicates that free radicals such as hydroxyl
radicals (oOH) and nitric oxide (oNO) may play opposite role in cell
and animal models of parkinsonism. oOH is a cytotoxic oxidant whereas
oNO is an atypical neuroprotective antioxidant. oNO and S-
nitrosoglutathione (GSNO) protect nigral neurons against oxidative
stress caused by 1-methyl-4-phenylpyridinium (MPP(+)), dopamine,
ferrous citrate, hemoglobin, sodium nitroprusside and peroxynitrite.
MPP(+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP), increases the nigral uptake of iron
complexes and dopamine overflow leading to the generation of oOH,
protein oxidation, lipid peroxidation, and associated retrograde
degeneration.
In addition to GSNO, MPP(+)-induced oxidative neurotoxicity can be
prevented by antioxidants including selegiline, 7-nitroindazole,
17beta-estradiol, melatonin, alpha-phenyl-tert-butylnitrone and
U78517F.
Similar to selegiline, 7-nitroindazole is a MAO-B inhibitor, which
blocks the bio-activation of MPTP and oxidative stress.
Freshly prepared but not light exposed, oNO-exhausted GSNO is about
100 times more potent than the classic antioxidant glutathione.
Via S-nitrosylation, GSNO also inhibits proteolysis and cytotoxicity
caused by caspases and HIV-1 protease. Furthermore, in addition to
protection against serum deprivation stress, the induction of neuronal
NOS1 in human cells increases tolerance to MPP(+)-induced neuro-
toxicity since newly synthesized oNO prevents apoptosis possibly
through up-regulation of bcl-2 and down regulation of p66(shc).
In conclusion, reactive oxygen species are unavoidable by-products of
iron-catalyzed dopamine auto-oxidation, which can initiate lipid
peroxidation, protein oxidation, DNA damage, and nigral loss, all of
which can be prevented by endogenous and exogenous oNO.
Natural and man-made antioxidants can be employed as part of
preventative or neuroprotective treatments in Parkinson's disease and
perhaps dementia complexes as well.
For achieving neuroprotection and neurorescue in early clinical
parkinsonian stages, a cocktail therapy of multiple neuroprotective
agents may be more effective than the current treatment with extremely
high doses of a single antioxidative agent.
Neurotoxicity research. [Neurotox Res]
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Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/634q5a
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
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