Lack of efficacy of curcumin on neurodegeneration in the mouse model of Niemann-Pick C1.
In order to determine the efficacy of curcumin in ameliorating symptoms of neurodegeneration in the mouse model of Niemann-Pick C1, a variety of formulations and dosages of curcumin, one comparable to one previously reported as efficacious, were provided orally to Npc1(-/-)mice. Plasma levels of curcumin, survival, tests of motor performance, and memory (in some cases) were performed. We found variable, but mild, increases in survival (1.5% to 18%). The greatest increased survival occurred with the highest dose (which was unformulated) while the control for the lipidated formulation (containing phosphatidylcholine and stearic acid) had an equivalent impact and other formulations, while not significantly increased, are also not statistically different in effect from the highest dose. We conclude that curcumin is not a highly efficacious treatment for neurodegeneration in Npc1(-/-) mice. Phosphatidylcholine and stearic acid should be studied further.
Dept. of Pediatrics, University of Arizona, Tucson, AZ, 85724-5073, United States.
Ivan A
IA
Borbon
Zach
Z
Hillman
Ernesto
E
Duran
Pawel R
PR
Kiela
Sally A
SA
Frautschy
Robert P
RP
Erickson
D000375:Aging / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000627:therapeutic use*; D004032:Diet; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids / Q000494:pharmacology; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000235:genetics; D008568:Memory / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D004856:Postural Balance / Q000187:drug effects; D013229:Stearic Acids / Q000494:pharmacology; D013534:Survival
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D014677:Pharmaceutical Vehicles; D010713:Phosphatidylcholines; D013229:Stearic Acids; C031183:stearic acid; D003474:Curcumin