Mice overexpressing 70-kDa heat shock protein show increased resistance to malonate and 3-nitropropionic acid.
Heat shock proteins (HSPs) are induced in response to oxidative stress, hypoxia-ischemia, and neuronal injury and play a protective role. Malonate and 3-nitropropionic acid (3-NP) are well-characterized animal models of Huntington's Disease (HD). They inhibit succinate dehydrogenase, inducing mitochondrial dysfunction, which triggers the generation of superoxide radicals, secondary excitotoxicity, and apoptosis. In this study, we examined whether the 70-kDa heat shock protein (HSP-70) is protective against neurotoxicity induced by malonate and 3-NP. Homozygous and heterozygous HSP-70 overexpressing mice (HSP-70+/+, HSP-70+/-) and wild-type controls received 3-NP or malonate and striatal lesion sizes were evaluated by stereology. Compared to HSP-70+/+ and HSP-70+/-, wild-type controls showed significantly larger striatal lesions following 3-NP or malonate injections. These findings support the idea that HSP-70 has a neuroprotective role that may be useful in the treatment of neurodegenerative diseases.
Dedeoglu
Alpaslan
A
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Ferrante
Robert J
RJ
Andreassen
Ole A
OA
Dillmann
Wolfgang H
WH
Beal
M Flint
MF
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D019610:Cytoprotection / Q000235:genetics / Q000502:physiology; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D019076:Transgenes
D018840:HSP70 Heat-Shock Proteins; D008314:Malonates; D009574:Nitro Compounds; D011422:Propionates; C030290:malonic acid; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid