title: MPTP-induced model of Parkinson's disease in heat shock protein 70.1             knockout mice.
abstract: Heat shock proteins (HSPs), molecular chaperones that assist in protein folding, have become a research focus in Parkinson's disease (PD) since the pathogenesis of PD is characterized by intracellular protein misfolding and inclusion body formation. This study investigated the effect of the knockout (KO) of the Hsp70.1 (approved gene symbol Hspa1b) gene on the sensitivity of murine nigrostriatal dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity. We confirmed changes in motor coordination and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra following MPTP treatment of C57BL/6 normal mice and Hspa1b KO mice. MPTP treatment led to motor control impairment and induced TH-positive dopaminergic neurodegeneration in normal mice. Compared to untreated normal mice, rotarod duration and the density of TH-positive neurons in the substantia nigra were also significantly lower in untreated KO mice (p<0.01). MPTP-treated KO mice had markedly decreased rotarod duration and reduced density of TH-positive neurons, compared to MPTP-treated normal mice. These results indicate that Hspa1b KO mice are more vulnerable to the neurotoxic effects of MPTP and are consistent with the hypothesis that HSPs represent an important molecular target for neuroprotective strategies in the treatment of PD.
authors.affiliation: Department of Emergency Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Park
authors.forename: Ah Rang
authors.initials: AR
authors.lastname: Cho
authors.forename: Seung Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Ban
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000201:enzymology; D018840:HSP70 Heat-Shock Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D009498:Neurotoxins; C081884:heat-shock protein 70.1; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase