Inducible nitric oxide synthase may be therapeutic target for
Parkinson's disease
WESTPORT, Dec 06, 1999 (Reuters Health) - Mice lacking the gene that
encodes the inducible isoform of nitric oxide synthase (iNOS) are more
resistant to experimental Parkinson's disease than wild-type
littermates.
These findings suggest that inhibitors of iNOS may effectively treat
Parkinson's disease, according to a report published in the December
issue of Nature Medicine.
Dr. Serge Przedborski, from Columbia University in New York, and
colleagues there and elsewhere in the US explain that according to
previous studies in mice and humans, neuronal NOS may not be the only
NOS isoform involved in the deterioration of dopamine-producing neurons
seen in Parkinson's disease.
Their aim in the present study was to determine whether or not iNOS was
involved in dopaminergic neurodegeneration induced by the neurotoxin
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in a mouse model of
Parkinson's disease..
According to the paper, MPTP treatment induced significant glial
activation in the mouse substantia nigra that was "...associated with
significant upregulation of inducible nitric oxide synthase."
The researchers also found that these changes "...preceded or paralleled
MPTP-induced dopaminergic neurodegeneration." This suggests, they say,
that nitric oxide and other radicals produced by activated microglial
cells may be responsible for neuronal cell loss.
Mice deficient in iNOS were significantly more resistant to MPTP-induced
dopaminergic cell loss than control mice, and they "...showed
significantly smaller increases in ventral midbrain nitrotyrosine
levels," a measure of peroxynitrite free radical production. The study
team notes, however, that the protective effect was confined to the
substantia nigra and was not observed in striatal nerve fibers.
Dr. Przedborski and his team conclude "...that inhibition of iNOS may be
a valuable target for the development of new therapies for [Parkinson's
disease] aimed at attenuating the actual loss of dopaminergic neurons."
They also suggest that "...the ideal therapeutic approach for
[Parkinson's disease] may require the combination of iNOS inhibitors
with other agents that have strong abilities in promoting nerve fiber
re-growth and in stimulating dopaminergic function as well as in
preserving dopaminergic nerve terminals."
In an accompanying News and Views article, Drs. Thomas Grunewald and M.
Flint Beal from Cornell University in New York say that the paper "...is
not only an important contribution to the elucidation of the
neurodegenerative process in idiopathic [Parkinson's disease], but also
suggests potential neuroprotective strategies."
The editorialists believe that different isoforms of NOS may act
together to cause neuronal injury in Parkinson's and other
neurodegenerative diseases.
Nat Med 1999;5:1354-1355,1403-1409.
1999 Reuters Limited.
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Judith Richards, London, Ontario, Canada
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Judith Richards, London, Ontario, Canada
[log in to unmask]
^^^^
\ /
\ | / Today’s Research
\\ | // ...Tomorrow’s Cure
\ | /
\|/
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