RGD Reference Report - Targeting oxidative stress, mitochondrial dysfunction and neuroinflammatory signaling by selective cyclooxygenase (COX)-2 inhibitors mitigates MPTP-induced neurotoxicity in mice.

General

Targeting oxidative stress, mitochondrial dysfunction and neuroinflammatory signaling by selective cyclooxygenase (COX)-2 inhibitors mitigates MPTP-induced neurotoxicity in mice.
Authors:	Gupta, A Kumar, A Kulkarni, SK
Citation:	Gupta A, etal., Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):974-81. Epub 2011 Feb 1.
RGD ID:	5687692
Pubmed:	PMID:21291942 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.pnpbp.2011.01.017 (Journal Full-text)
Several studies have pointed towards the role of oxidative stress, mitochondrial dysfunction and neuroinflammation in Parkinson's disease (PD). The present study was focused on the possible neuroprotective effect of selective cyclooxygenase (COX)-2-inhibitors: valdecoxib and NS-398 in 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP)-induced neurotoxicity in mice. MPTP administration in dose of 40 mg/kg, i.p (four injections of 10mg/kg, i.p. at an interval of 1h each) significantly induced the Parkinson-like symptoms in mice as indicated by change in locomotor activity, inability to correct posture (bar test), and oxidative stress (increased levels of lipid peroxidation, nitrite concentration, and depletion of antioxidant enzyme). MPTP administration significantly impaired mitochondrial complex-I activity and redox activity, upregulated the caspase-3 and NF-kappaB levels as compared to vehicle group. Treatment with valdecoxib (5 or 10 mg/kg, p.o.) or NS-398 (5 or 10mg/kg, p.o.) for 7 days significantly reversed behavioral, biochemical, mitochondrial complex alterations as well as attenuated the induction of proinflammatory mediators in MPTP-treated groups. The findings of the present study substantiate the neuroprotective role of selective COX-2 inhibitors in ameliorating MPTP-induced neurodegeneration in mice and suggest the possible therapeutic potential of these drugs in the management of PD.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Parkinson's disease		ISO	mt-Nd3 (Mus musculus)	5687692; 5687692	protein: decreased activity: brain: MPTP model of Parkinson disease	RGD
Parkinson's disease		IMP		5687692	protein: decreased activity: brain: MPTP model of Parkinson disease	RGD

Objects Annotated

Genes (Rattus norvegicus)

Mt-nd3 (mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 3)

Genes (Mus musculus)

mt-Nd3 (NADH dehydrogenase 3, mitochondrial)

Genes (Homo sapiens)

MT-ND3 (mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 3)

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Targeting oxidative stress, mitochondrial dysfunction and neuroinflammatory signaling by selective cyclooxygenase (COX)-2 inhibitors mitigates MPTP-induced neurotoxicity in mice.