Neuroprotective Effect of Demethylsuberosin, a Proteasome Activator, against MPP⁺-induced Cell Death in Human Neuroblastoma SH-SY5Y Cells

Abstract

Demethylsuberosin isolated from the roots of Cudrania tricuspidata demonstrated a potent proteasome activator by enhancing all three chymotrypsin-like, trypsin-like, and caspase-like proteasome activities in a 20S proteasome activity assay. It also attenuated the 1-methyl-4-phenylpyridinium-induced dysfunction of the chymotrypsin-like and caspase-like activities of proteasome in SH-SY5Y cells with EC₅₀ values of 0.76 µM and 0.82 µM, respectively. Additionally, demethylsuberosin protected neuronal cells against 1-methyl-4-phenylpyridinium-induced cell death with an EC₅₀ value of 0.17 µM, while the EC₅₀ value of betulinic acid was 4.29 µM. We are reporting that demethylsuberosin is a potent proteasome activator with a neuroprotective effect, suggesting a possible candidate for the protection or treatment of neurodegenerative diseases such as Parkinsonʼs disease.

Key words

Cudrania tricuspidata - Moraceae - demethylsuberosin - neuroprotection - proteasome activator - 1-methyl-4-phenylpyridinium (MPP⁺)

• References

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