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PLoS One. 2015 Jun 2;10(6):e0128510. doi: 10.1371/journal.pone.0128510. eCollection 2015.

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

Author information

1
Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America.
2
Research Services, Veterans Affairs Medical Center, Portland, Oregon, United States of America; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, United States of America.
3
Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America.
4
Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America; Parkinson Center of Oregon, Oregon Health & Science University, Portland, Oregon, United States of America.

Abstract

The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of α-synuclein protein in vitro, yet no studies have described the interaction of curcumin and α-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 α-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of α-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated α-synuclein in terminals, but had no direct effect on α-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.

PMID:
26035833
PMCID:
PMC4452784
DOI:
10.1371/journal.pone.0128510
[Indexed for MEDLINE]
Free PMC Article

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