TY - JOUR
T1 - Curcumin treatment improves motor behavior in α-synuclein transgenic mice
AU - Spinelli, Kateri J.
AU - Osterberg, Valerie R.
AU - Meshul, Charles K.
AU - Soumyanath, Amala
AU - Unni, Vivek K.
PY - 2015/6/2
Y1 - 2015/6/2
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0128510
DO - 10.1371/journal.pone.0128510
M3 - Article
C2 - 26035833
AN - SCOPUS:84934894524
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 6
M1 - e0128510
ER -