Curcumin Treatment Improves Motor Behavior in ?-Synuclein Transgenic Mice.

ABSTRACT: The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of ?-synuclein protein in vitro, yet no studies have described the interaction of curcumin and ?-synuclein in genetic synucleinopathy mouse models. Here we examined the effect of chronic and acute curcumin treatment in the Syn-GFP mouse line, which overexpresses wild-type human ?-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of ?-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated ?-synuclein in terminals, but had no direct effect on ?-synuclein aggregation, as measured by in vivo multiphoton imaging and Proteinase-K digestion. Using LC-MS/MS, we detected ~5 ng/mL and ~12 ng/mL free curcumin in the plasma of chronic or acutely treated mice, with a glucuronidation rate of 94% and 97%, respectively. Despite the low plasma levels and extensive metabolism of curcumin, these results show that dietary curcumin intervention correlates with significant behavioral and molecular changes in a genetic synucleinopathy mouse model that mimics human disease.

SUBMITTER: Spinelli KJ 

PROVIDER: S-EPMC4452784 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature