Melatonin ameliorated okadaic-acid induced Alzheimer-like lesions.
OBJECTIVE
To explore the protective effects of melatonin (Mel) on the abnormal phosphorylation of neuronal cytoskeletal proteins.


METHODS
We generated a neuroblastoma (SH-SY5Y) cell system in which cytoskeletal proteins are abnormally phosphorylated resulting in microtubule disruption due to the marked inhibition of protein phosphatase activities by okadaic acid (OA).


RESULTS
OA-induced declines in cell viability and mitochondrial metabolic activity were remarkably prevented by Mel. In addition, the hyperphosphorylation/accumulation of neurofilament-(NF-) H/M subunits and the disruption of microtubules, induced by OA, were significantly inhibited by Mel.


CONCLUSIONS
Our results suggest multiple protective functions of Mel against a series of pathological lesions known to culminate in AD, including abnormal phosphorylation of cytoskeletal proteins, microtubule disassembly and mitochondrion-initiated cell toxicity.
Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yi-peng
YP
Wang
Xian-tao
XT
Li
Shi-jie
SJ
Liu
Xin-wen
XW
Zhou
Xiao-chuan
XC
Wang
Jian-zhi
JZ
Wang
D000544:Alzheimer Disease / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured
D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D019319:Okadaic Acid; D008550:Melatonin