Does ORP150/HSP12A protect dopaminergic neurons against MPTP/MPP(+)-induced neurotoxicity?
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its metabolite 1-methyl-4-phenylpyridinium (MPP(+)) are drugs that are widely used in experimental Parkinson disease (PD) models. What is the significance of ORP150/HSP12A, a molecular chaperone in the endoplasmic reticulum (ER), in the nigrostriatal system? Dopaminergic neuroblastoma SH-SY5Y cells and dopaminergic neurons of the substantia nigra pars compacta (SNpc) were examined. Our observations led to the hypothesis that ORP150 protects against MPTP/MPP(+)-induced neurotoxicity, and indicate the importance of the ER environment in maintaining the nigrostriatal pathways.
Kitao
Yasuko
Y
Department of Neuroanatomy Kanazawa University Graduate School of Medical Science, Ishikawa, Japan. kitao@nanat.m.kanazawa-u.ac.jp
Matsuyama
Tomohiro
T
Takano
Katsura
K
Tabata
Yoshiyuki
Y
Yoshimoto
Tanihiro
T
Momoi
Takashi
T
Yamatodani
Atsushi
A
Ogawa
Satoshi
S
Hori
Osamu
O
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D004298:Dopamine / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014161:Transduction, Genetic
D018840:HSP70 Heat-Shock Proteins; D011506:Proteins; C050087:oxygen-regulated proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine