Potential therapeutic effects of curcumin: relationship to microtubule-associated proteins 2 in Aβ1-42 insult.
Curcumin can bind senile plaques and promote disaggregation of existing amyloid deposits and prevent aggregation of new amyloid deposits. Curcumin can also reverse distorted and curvy neurites around senile plaques and repair the neuritic abnormalities. We hypothesized whether altered neurite morphologies resulting from Aβ production had anything to do with the changes of expression of microtubule-associated protein 2 (MAP2), but curcumin could reverse damaged neurites by upregulation of MAP2 expression. In present study we designed and chemically synthesized curcumin and its six derivatives. After screening the protective effect of curcumin and derivatives, we found that the viability of SK-N-SH cell model induced by Aβ1-42 was significantly increased by curcumin and Cur1, and the expression of MAP-2 protein was obviously up-regulated in immunocytochemical staining and Western blot. The cell morphologies, including the number of neurites, neurite growth and neurite extension, were significantly improved. Cur1 showed more significant protective effect on SK-N-SH cells than curcumin. Our study revealed for the first time that the neuroprotective effect of curcumin and curcumin derivatives not only directly depends on their special chemical constitution, but they can resist to Aβ damage by up-regulation of MAP-2 expression. In view of the special advantages of curcumin and Cur1, we reasonably believe that curcumin and Cur1 may be considered as an ideal therapeutic agent for the treatment of AD.
Xiao
Zijian
Z
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Lin
Liming
L
Liu
Zhonghua
Z
Ji
Fengtao
F
Shao
Weiyan
W
Wang
Minjuan
M
Liu
Ling
L
Li
Shengliang
S
Li
Feng
F
Bu
Xianzhang
X
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects
D016229:Amyloid beta-Peptides; C556037:Cur1 compound; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003474:Curcumin