Curcumin prevents dopaminergic neuronal death through inhibition of the c-Jun N-terminal kinase pathway.
Recent studies have shown that the c-Jun N-terminal kinase (JNK) signaling pathway is involved in dopaminergic neuronal degeneration, and direct blockade of JNK by specific inhibitors may prevent or effectively slow the progression of Parkinson disease (PD). Previous studies have revealed that the natural phenolic compound curcumin can reduce inflammation and oxidation, which makes it a potential therapeutic agent for neurodegenerative diseases. In this study, we investigated whether curcumin protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP) or 1-methyl-4-phenylpyridnium ion- (MPP(+)) induced dopaminergic neurotoxicity in C57BL/6N mice or SH-SY5Y cells by inhibiting JNK pathways both in vivo and in vitro. Curcumin treatment significantly improved behavioral deficits, and enhanced the survival of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) in the MPTP-induced PD model mice. Most importantly, curcumin treatment significantly inhibited MPTP/MPP(+)-induced phosphorylation of JNK1/2 and c-Jun, and cleaved caspase-3. Our study suggests that the neuroprotective effect of curcumin is not related simply to its antiinflammatory and antioxidant properties, but involves other mechanisms, particularly by targeting the JNK pathways.
Key Laboratory of Cell Biology of Ministry of Public Health of China, Laboratory of Cell Engineering and Therapy of Institute of Tissue Engineering, China Medical University, Shenyang, PR China.
Song
S
Yu
Wei
W
Zheng
Na
N
Xin
Zhi-Hong
ZH
Chi
Nai-Qian
NQ
Wang
Ying-Xue
YX
Nie
Wan-Yu
WY
Feng
Zhan-You
ZY
Wang
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D016755:Proto-Oncogene Proteins c-jun; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D003474:Curcumin; D004298:Dopamine