Resistance to striatal dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice expressing human mutant Cu,Zn superoxide dismutase.
Recent data indicate that overexpression of the enzyme Cu,Zn superoxide dismutase (SOD1) in mice confers neuroprotection against various dopamine neurotoxins like 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), methamphetamine, 6-hydroxydopamine and methylenedioxymethamphetamine. In the present study we investigated whether a mutant form of SOD1 (G93A), occurring in humans affected by amyotrophic lateral sclerosis, leads to a differential vulnerability of nigrostriatal dopaminergic neurons to the chronic dopamine depletion induced by the selective neurotoxin MPTP. Our results indicate that overexpression of both wild-type and human mutant SOD1 induces comparable neuroprotective effects against striatal dopaminergic depletion.
Fornai
Francesco
F
Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
Carrì
Maria Teresa
MT
Ferri
Alberto
A
Paolucci
Egle
E
Prisco
Simona
S
Bernardi
Giorgio
G
Rotilio
Giuseppe
G
Mercuri
Nicola Biagio
NB
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency*; D015259:Dopamine Agents / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
D015259:Dopamine Agents; D018696:Neuroprotective Agents; D009498:Neurotoxins; C000606290:SOD1 protein, human; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D004298:Dopamine